Programs & Groups

Please click on the corresponding programs below

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Josep Tabernero

Director, Clinical Research Program
Biosketch

“Our patients and VHIO's multidisciplinary approach to driving advances against cancer are at the center of everything we do. Incorporating exceptionally talented groups and taskforces, VHIO's Clinical Research Program follows three guiding principles, namely, predictive, proven and precise. We develop novel agents and approaches to diagnose cancer earlier and better predict response to therapy in order to deliver optimal and personalized treatments to the right patients at the right time, on time.”

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VHIO's multidisciplinary and translational approach to research closely connects its researchers with our clinical investigators and in so doing, enables our Program to spearhead cooperative preclinical, early phase studies aimed at developing novel therapeutics, as well as new or redefined prognostic/diagnostic tools to better detect disease, track progression and more accurately predict response to anti-cancer therapies.

We pioneer novel study design including Baskets and first-in-human trials. Concerning the former, our Cancer Core Europe endorsed Basket of Baskets (BoB) trial's protocol of its first module, Immune-Checkpoint Blockade in Genomically Selected Populations, was approved this year. An example of VHIO's contribution to the latter, a study led by Cristina Saura, PI of our Breast Cancer and Melanoma Group (Saura et al. Cancer Discov), showed that the potent inhibition of AKT signaling with AKT inhibitor, ipatasertib, was associated with a tolerable safety profile and meaningful disease control in patients with diverse solid tumors who progressed on prior therapies with many of their tumors manifesting activation of AKT. These findings promise new therapeutic opportunity for the treatment of this subpopulation of patients.

We have continued to develop next generation blood-based diagnostics to monitor disease, its respective molecular specificities, and response to novel targeted therapies. More specifically, we continue to employ our in-house BEAMing digital PCR/flow cytometry technology to evaluate patients with metastatic colorectal cancer.

Importantly too, thanks to funding received from the FERO Foundation, we have incorporated our Droplet Digital PCR (ddpCR) Bio-Rad Technology platform which has enabled us to develop panels to detect mutations in EGFR in patients with lung cancer and AKT1, PIK3CA and ESR1 in breast cancer patients. We are making significant progress in validating and developing this technology for the more effective, less invasive ‘policing’ of cancer over time, real time.

As a reflection of our expertise in developing liquid biopsy, in collaboration with our Cancer Genomics Group directed by Ana Vivancos, we counted two projects awarded under the TRANSCAN Joint Translational Call on Minimally and non-invasive methods for early detection and/or progression of cancer. The first will establish non-invasive prognostic markers for resected early stage non-small cell lung cancer by assessing the role of circulating and exosomal miRNAs and free circulating DNA (fcDNA). The second will focus on the early detection of relapse in advanced colon cancer patients by longitudinally following a personalized signature by liquid biopsy.

Cancer immunotherapy continues to show much promise as a firm contender in dismantling cancer's armory. We at VHIO are dedicated to potentiating novel immune agents as mono therapy or in combination as well as accelerating insights into the cellular and molecular mechanisms modulating immune response.

We have launched our Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI) supported by the BBVA Foundation, in collaboration with colleagues at the Memorial Sloan Kettering Cancer Center – MSKCC (New York). As a renewal of our framework agreement, CAIMI aims to advance agents that inhibit checkpoint regulation of the immune system, establish the mechanisms of resistance and response to these therapies, and prioritize the early development of those agents showing most promise. In partnership with MSKCC, we will co-found and develop six translational projects linked to the early clinical development phases of immunotherapy.

This year also celebrated the renewal of our Obra Social ”la Caixa” International Program for Cancer Research and Education. This initiative will further pursue the established synergies between VHIO and MSKCC, and spur the development of several new research lines including the pan-omic exploration (genomics and radiomics) of solid tumors with particular emphasis on Big Data. We will explore the impact of gene mutations in DNA damage repair and metastatic prostate cancer together with data mining to expose the molecular genetic determinants of sensitivity to targeted therapies in solid cancers.

Talking of Big Data, as a result of our leading research in cancer classification performed by our Oncology Data Science (ODysSey) Group, led by Rodrigo Dienstmann, we published a review article (Dienstmann et al. Nat Rev Cancer, 2017), underlining the challenges and opportunities ahead in putting the brakes on the molecular culprits that drive tumor initiation, development and growth in each established individual consensus molecular subtype of colorectal cancer. As this Report goes to print I am pleased to announce that VHIO has been accepted to participate in AACR's Project Genomics Evidence Neoplasia Information Exchange (GENIE).

To better understand how major molecular alterations support the irrepressible growth of tumors, findings from a muli-center study (Zabala-Letona et al. Nature. 2017) led by colleagues at CIC bioGune (Bizkaia, the Basque Country), in collaboration with VHIO groups and several others, including MSKCC, revealed a mechanism through which prostate cancer produces metabolites essential for tumor biology to thrive. Evidencing that mTORC1-dependent AMD1 regulation sustains polyamine metabolism in this tumor type, this study supports the metabolic characterisation of cancer as an innovative approach to identify new ways to effectively treat disease.

We also advance cancer discovery and therapeutics in partnership through various international consortia and networks of excellence (click here). In colorectal cancer, we coordinate the EU H2020 funded MoTriColor Consortium which focuses on validating three novel therapeutic approaches linked to three gene expression signatures. In 2017, we initiated the prescreening of patients from the different clinical sites and next year we will start enrolling patients in the three MoTriColor clinical trials.

‘At home’, combining expertise with several other leading research centers across Catalonia, we are now participating in the pilot testing of the implementation and application of comprehensive genomics to clinical decision making in the treatment and care of our patients. Led by Elías Campo (Pi i Sunyer Biomedical Research Institute – IDIBAPS, and Hospital Clínic), with myself as PI, this project is supported by the Catalan Strategic Plan for Health Research and Innovation (PERIS) to promote people centered health research.

I believe in forging closer collaborations with other specialties and engaging the entire oncology ecosystem. Only by considering and responding to the needs of all stakeholders in oncology including patients and their families, researchers, payers, regulators, the policymakers, and industry, will we accelerate our dedicated efforts aimed at solving cancer sooner.

We can and will do better.

Clinical Research Groups

Please click on the corresponding groups below

Breast Cancer & Melanoma
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Cristina Saura
Principal Investigator
Early Clinical Drug Development
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Elena Garralda
Principal Investigator
Gastrointestinal & Endocrine Tumors
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Josep Tabernero
Principal Investigator
Gynecological Malignacies
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Ana Oaknin
Principal Investigator
High Risk & Cancer Prevention
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Judith Balmaña
Principal Investigator
Oncogenetics
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Orland Díez
Principal Investigator
Oncology Data Science (ODysSey)
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Rodrigo Dienstmann
Principal Investigator
Radiation Oncology
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Jordi Giralt
Principal Investigator
Thoracic Tumors & Head and Neck Cancer
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Enriqueta Felip
Principal Investigator

Breast Cancer & Melanoma Group

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Principal Investigators
Cristina Saura

Associate Translational Investigators
Javier Cortés
Isabel Rubio

Medical Oncologists and Clinical Fellows
Miriam Arumí
Analía Azaro
Judith Balmaña
Meritxell Bellet
Marta Capelan
Cristina Cruz
Santiago Ignacio Escrivà
Laia Garrigós
Patricia Gómez
Eva Muñoz
Mafalda Oliveira
Carolina Ortiz
Beatriz Rojas
Esther Zamora

Clinical Nurse Specialist
Anna Suñol

Nutritionist
Nuria Durán

SUMMARY

Our Breast Cancer & Melanoma Group is one of the most active and renowned in Europe. In 2017 our group published a total of 29 papers with a cumulative Impact Factor (IF) of 287,28. We are not only committed to participating in clinical trials, but also lead many of them; reflected by our representation on several Steering Committees. We apply translational data to help both guide and accelerate the clinical development of anti-cancer compounds.

Our key areas of interest include:

HER-positive disease: we continue to participate in major trials testing novel therapies, and recruit patients in clinical studies with the most promising agents including neratinib, margetuximab, tucatinib, SYD985, DS8201 and MCLA128. We also treat patients in combination therapy trials that are designed to overcome mechanisms of resistance such as trastuzumab plus palbociclib or abemaciclib. In collaboration with VHIO's Growth Factors Group, led by Joaquín Arribas, we continue to explore cancer drug resistance to these therapies.

Discovery of novel mechanisms of resistance: In close collaboration with VHIO's Experimental Therapeutics Group, headed by Violeta Serra, we have developed several PDX models to advance insights into the mechanisms of resistance in breast cancer that may be overcome by treatment with PI3K inhibitors. Our group has established expertise in triple negative breast cancer and BRCA tumors thanks to our broad program focused on the evaluation of immunotherapies and various PARP inhibitors in the clinic combined with translational research of excellence in both areas. In hormone receptor-positive disease we are leading different trials using the most novel compounds (PI3K-AKT-mTOR, CDK4/6 inhibitors and BET inhibitors), and have observed encouraging activity of neratinib in tumors harboring HER2 mutations.

New compounds: an emerging group of drugs known as immunoconjugates are undoubtedly here to stay. Their innovative design makes them extremely active given that chemotherapy is released specifically inside the tumor with increased potency and less toxicity. We are pleased to report that we have already treated patients with SYD-985, CDX011, SAR566658, and very soon, with IMMU-132.

cfDNA: In collaboration with VHIO's Cancer Genomics Group, led by Ana Vivancos, we are analyzing tumor tissue and cfDNA that will, in the near future, provide crucial insights into the evolution of genetic alterations of tumors both in the advanced setting as well as the challenging scenario of early disease.

Our Melanoma Group is led by Eva Muñoz, also Medical Oncologist and Clinical Fellow of our group, and has made significant progress throughout 2017 by actively participating in several phase I, II and III clinical trials focused on melanoma and other skin tumors to study several emerging therapies in metastatic and adjuvant cancer treatment. The group has consolidated its own research program incorporating clinical investigators and cancer researchers at VHIO. Collectively, we conduct purely translational research centered on melanoma acquisition and progression towards developing new treatment options for our patients.

STRATEGIC GOALS

  • Optimize therapies with the introduction of novel anti-cancer therapies and addition of rational combinations to overcome mechanisms of resistance.
  • Incorporate proteomics, genomics, and circulating tumor cell platforms in translational research to advance insights into tumor biology.
  • Apply preclinical, predictive data to help guide innovative clinical trial design in advanced disease.
  • Participate in clinical studies and projects for the collection of clinical and biological data from patients in order to ultimately improve outcomes.

HIGHLIGHTS

  • We have published practice-changing data in the field of adjuvant and metastatic breast cancer.
  • Thanks to our collaboration with various clinical departments at the Vall d'Hebron University Hospital (HUVH), our group has become one of the most active in neoadjuvant and metastatic breast cancer studies worldwide, set firmly within the context of translational research.
  • VHIO has established itself as a reference center in developing patient-derived xenografts (PDX) and we are currently expanding our collection of these models. We are also consolidating our cfDNA program for genotyping in breast cancer.
  • In melanoma, our group is one of the largest networks in Spain and across Europe, and one of the most active in metastatic and adjuvant studies in melanoma. Each trial is tightly connected with the corresponding translational research led by VHIO.

PI PAPER PICK (full list for 2017 below)

Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discov. 2017 Jan;7(1):102-113.

Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Apr;18(4):545-554.

Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224.

Pérez-Alea M, McGrail K, Sánchez-Redondo S, Ferrer B, Fournet G, Cortés J, Muñoz E, Hernandez-Losa J, Tenbaum S, Martin G, Costello R, Ceylan I, Garcia-Patos V, Recio JA. ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment. Oncogene. 2017 Oct 12;36(41):5695-5708.

HORIZONS 2018

    Breast cancer:
  • Ensure that our Breast Cancer Unit continues to be a reference site for the treatment of patients in clinical trials with novel anti-cancer therapies.
  • Use cfDNA as a potential tool for detection of molecular alterations in real time to more effectively track tumoral heterogeneity and clonal evolution in breast cancer.
  • Optimize clinical and preclinical research based on patient-derived xenografts (PDX).
  • Lead novel and ‘smarter’ clinical trials with particular focus on targeted agents.
  • Consolidate strategic alliances with the most prestigious cancer research centers across Europe to work on independent clinical and preclinical studies.
  • Achieve a better understanding on how chemotherapy affects the fetus in pregnant patients.
  • Better understand tumor immunology in breast cancer.

  • Melanoma:
  • Consolidate the Cutaneous Tumor Unit as reference center for melanoma and other cutaneous tumors through an established referral network and participation in major clinical trials.
  • Involvement in the early drug development and design of different clinical trials in melanoma and other skin tumors.
  • Expand our collaboration with VHIO researchers to better understand tumor immunology in melanoma, identify biomarkers of tumor progression, and validate novel therapeutic targets in melanoma.
  • Formation of a seroteca to collect samples for future national and international collaborations.

PUBLICATIONS

  1. Başaran GA, Twelves C, Diéras V, Cortés J, Awada A. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer.Cancer Treat Rev. 2017 Dec 6;63:144-155
  2. Cortés J, Im SA, Holgado E, Perez-Garcia JM, Schmid P, Chavez-MacGregor M. The next era of treatment for hormone receptor-positive, HER2-negative advanced breast cancer: Triplet combination-based endocrine therapies.Cancer Treat Rev. 2017 Dec;61:53-60
  3. de Melo Gagliato D, Cortes J, Curigliano G, Loi S, Denkert C, Perez-Garcia J, Holgado E. Tumor-infiltrating lymphocytes in Breast Cancer and implications for clinical practice.  Biochim    Biophys Acta. 2017 Dec;1868(2):527-537.
  4. Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, Belen García A, Martínez-Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA. Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun. 2017 Nov 2;8(1):1278.
  5. Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.Lancet Oncol. 2017 Oct;18(10):1360-1372.
  6. Rugo HS, Trédan O, Ro J, Morales SM, Campone M, Musolino A, Afonso N, Ferreira M, Park KH, Cortes J, Tan AR, Blum JL, Eaton L, Gause CK, Wang Z, Im E, Mauro DJ, Jones MB, Denker A, Baselga J. A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer.Breast Cancer Res Treat. 2017 Oct;165(3):601-609.
  7. Pérez-Alea M, McGrail K, Sánchez-Redondo S, Ferrer B, Fournet G, Cortés J, Muñoz E, Hernandez-Losa J, Tenbaum S, Martin G, Costello R, Ceylan I, Garcia-Patos V, Recio JA. ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment. 2017 Oct 12;36(41):5695-5708.
  8. Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer.Clin Cancer Res. 2017 Sep 1;23(17):5218-5224.
  9. Vega JF, Ramos J, Cruz VL, Vicente-Alique E, Sánchez-Sánchez E, Sánchez-Fernández A, Wang Y, Hu P, Cortés J, Martínez-Salazar J. Molecular and hydrodynamic properties of human epidermal growth factor receptor HER2 extracellular domain and its homodimer: Experiments and multi-scale simulations.Biochim Biophys Acta. 2017 Sep;1861(9):2406-2416.
  10. Saha P, Regan MM, Pagani O, Francis PA, Walley BA, Ribi K, Bernhard J, Luo W, Gómez HL, Burstein HJ, Parmar V, Torres R, Stewart J, Bellet M, Perelló A, Dane F, Moreira A, Vorobiof D, Nottage M, Price KN, Coates AS, Goldhirsch A, Gelber RD, Colleoni M, Fleming GF; SOFT; TEXT Investigators; International Breast Cancer Study Group. Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials.J Clin Oncol. 2017 Sep 20;35(27):3113-3122
  11. Cortés J, Rugo HS, Awada A, Twelves C, Perez EA, Im SA, Gómez-Pardo P, Schwartzberg LS, Diéras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, O'Shaughnessy J. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017 Sep;165(2):329-341
  12. Mancebo G, Sole-Sedeno JM, Pino O, Miralpeix E, Mojal S, Garrigos L,Lloveras B, Navarro P, Gibert J, Lorenzo M, Aran I, Carreras R, Alameda F. Prognostic impact of CD133 expression in Endometrial Cancer Patients.Sci Rep. 2017 Aug 9;7(1):7687.
  13. Muñoz-Couselo E, Adelantado EZ, Ortiz C, García JS, Perez-Garcia J. NRAS-mutant melanoma: current challenges and future prospect.Onco Targets Ther. 2017 Aug 8;10:3941-3947. Review.
  14. Baselga J, Im SA, Iwata H, Cortés J,De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M.Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol. 2017 Jul;18(7):904-916.
  15. González-Cao M, Arance A, Piulats JM, Marquez-Rodas I, Manzano JL, Berrocal A, Crespo G, Rodriguez D, Perez-Ruiz E, Berciano M, Soria A, Castano AG, Espinosa E, Montagut C, Alonso L, Puertolas T, Aguado C, Royo MA, Blanco R, Rodríguez JF, Muñoz E, Mut P, Barron F, Martin-Algarra S; Spanish Melanoma Group. Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. Clin Transl Oncol. 2017 Jun;19(6):761-768
  16. Baselga J, Morales SM, Awada A, Blum JL, Tan AR, Ewertz M, Cortes J, Moy B, Ruddy KJ, Haddad T, Ciruelos EM, Vuylsteke P, Ebbinghaus S, Im E, Eaton L, Pathiraja K, Gause C, Mauro D, Jones MB, Rugo HS. A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer.Breast Cancer Res 2017 Jun;163(3):535-544
  17. Peg V, Sansano I, Vieites B, Bernet L, Cano R, Córdoba A, Sancho M, Martín MD, Vilardell F, Cazorla A, Espinosa-Bravo M, Pérez-García JM, Cortés J, Rubio IT, Ramón Y Cajal S. Role of total tumour load of sentinel lymph node on survival in early breast cancer patients. 2017 Jun;33:8-13
  18. Maetens M, Brown D, Irrthum A, Aftimos P, Viale G, Loibl S, Laes JF, Campbell PJ, Thompson A, Cortes J, Seiler S, Vinnicombe S, Oliveira M, Rothé F, Bareche Y, Fumagalli D, Zardavas D, Desmedt C, Piccart M, Loi S, Sotiriou C. The AURORA pilot study for molecular screening of patients with advanced breast cancer-a study of the breast international group.NPJ Breast Cancer. 2017 Jun 29;3:23.
  19. Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Castellà E, Nellist M, Morales S, Valls J, Velasco A, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EEW, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JWM, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR, Pujana MA. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition. 2017 May 11;36(19):2737-2749.
  20. Twelves C, Cortés J, O'Shaughnessy J, Awada A, Perez EA, Im SA, Gómez-Pardo P, Schwartzberg LS, Diéras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Rugo HS. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial.Eur J Cancer. 2017 May;76:205-215.
  21. Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial.Lancet Oncol. 2017 Apr;18(4):545-554
  22. Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab.Ann Oncol. 2017 Apr 1;28(4):761-768
  23. Quintela-Fandino M, Soberon N, Lluch A, Manso L, Calvo I, Cortes J, Moreno-Antón F, Gil-Gil M, Martinez-Jánez N, Gonzalez-Martin A, Adrover E, de Andres R, Viñas G, Llombart-Cussac A, Alba E, Mouron S, Guerra J, Bermejo B, Zamora E, García-Saenz JA, Simon SP, Carrasco E, Escudero MJ, Campo R, Colomer R, Blasco MA. Critically short telomeres and toxicity of chemotherapy in early breast cancer. 2017 Mar 28;8(13):21472-21482.
  24. Quintela-Fandino M, Lluch A, Manso L, Calvo I, Cortes J, García-Saenz JA, Gil-Gil M, Martinez-Jánez N, Gonzalez-Martin A, Adrover E, de Andres R, Viñas G, Llombart-Cussac A, Alba E, Guerra J, Bermejo B, Zamora E, Moreno-Anton F, Pernas Simon S, Carrato A, Lopez-Alonso A, Escudero MJ, Campo R, Carrasco E, Palacios J, Mulero F, Colomer R. 18F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial.Clin Cancer Res. 2017 Mar 15;23(6):1432-1441
  25. Hierro C, Azaro A, Argilés G, Elez E, Gómez P, Carles J, Rodon J. Unveiling changes in the landscape of patient populations in cancer early drug development. Oncotarget. 2017 Feb 21;8(8):14158-14172.
  26. Cardoso F, Harbeck N, Barrios CH, Bergh J, Cortés J,El Saghir N, Francis PA, Hudis CA, Ohno S, Partridge AH, Sledge GW, Smith IE, Gelmon KA. Research needs in breast cancer.Ann Oncol. 2017 Feb 1;28(2):208-217
  27. Sharma P, López-Tarruella S, García-Saenz JA, Ward C, Connor CS, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Del Monte-Millán M, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortes J,Fuentes Rivera H, Bretel Morales D, Márquez-Rodas I, Perou CM, Wagner JL, Mammen JM, McGinness MK, Klemp JR, Amin AL, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts.Clin Cancer Res. 2017 Feb 1;23(3):649-65
  28. Musolino A, Campone M, Neven P, Denduluri N, Barrios CH, Cortes J, Blackwell K, Soliman H, Kahan Z, Bonnefoi H, Squires M, Zhang Y, Deudon S, Shi MM, André F. Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2- breast cancer that had progressed during or after prior endocrine therapy.Breast Cancer Res. 2017 Feb 10;19(1):1
  29. Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors.Cancer Discov. 2017 Jan;7(1):102-113.

PROJECTS

  • Molecular screening platform for patients with advanced or metastatic breast cancer. SOLTI 1301-AGATA
  • Investigation of molecular alterations in metastatic breast cancer. AURORA
  • POSITIVE: Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine treatment
  • PREDICOP: Prevención de las recaídas mediante ejercicio, dieta y control de peso en pacientes con cáncer de mama.
  • BRCA-RES: Estudio de mecanismos genéticos de resistencia a terapias dirigidas.
  • Desvelando las vías moleculares que llevan al desarrollo de la carcinomatosis leptomeníngea.
  • Impacto del test Oncotype DX® para cáncer de mama en las decisiones de tratamiento en pacientes. ONCOTEST KARMA DX
  • Efectividad en la Neoadyuvancia de la teràpia basada en el doble bloqueo con pertuzumab y trastuzumab , en pacientes HER2 positivas en la práctica clínica habitual.(NEOPETRA)
  • Detección de marcadores de muerte celular en pacientes con cáncer de mama tratadas con quimioterapia preoperatoria
  • Control del estrés oxidativo en pacientes con cáncer de mama diagnosticado durante el embarazo
  • AMBER: Estudio observacional retrospectivo del tratamiento con nab-paclitaxel (Abraxane®) en pacientes con cáncer de mama metastásico en la práctica clínica habitual
  • Estudio traslacional de determinación en suero y plasma de BRAFV600 en pacientes con melanoma metastásico BRAFV600.
  • Nueva tecnología para la detección de mutaciones puntuales en el oncogen BRAF a partir de sangre periférica y su validación en muestras tisulares/tumorales en pacientes afectos de melanoma metastásico.
  • Biopsia líquida para detección nanoplasmónica de exosomas: prediciendo respuesta a la inmunoterapia.
  • Perfil epigenético capaz de predecir la respuesta a inmunoterapia en melanoma.
  • 360º RESISTANCE: Aplicación de un modelo de investigación traslacional para estudiar predictores de respuesta/toxicidad, y mecanismos de resistencia en pacientes tratados con inmunoterapia
  • Brain-specific strategies to improve responses to immunotherapy.

AWARDS

  • La Generalitat de Catalunya´s Strategic plan for research and innovation in health (PERIS) and support for the intensification of research activities.
  • Awarded project: Precision medicine in metastatic breast cancer: determination of mutations in tumors and circulating tumor DNA (ctDNA) as a guide for the treatment of the patients with metastatic breast cancer.

Early Clinical Drug Development Group

Imagen

Director of Clinical Research at VHIO
Josep Tabernero

Principal Investigator, Early Clinical Drug Development Group. Executive Director, Research Unit for Molecular Therapy of Cancer (UITM) – "la Caixa"
Elena Garralda

Associate Investigators
Senior Consultants

Judith Balmaña
Joan Carles
Enriqueta Felip
Teresa Macarulla
Ana Oaknin
Cristina Saura

Phase I Investigators
Maria Alsina
Guillermo Argilés
Analía B. Azaro
Irene Braña
Marta Capelan
Cristina Cruz
Maria Elena Élez
Santiago Ignacio Escrivá
Lorena Fariñas
Patricia Gómez
Jorge Hernando
Cinta Hierro
Juan Jesús Martín Liberal
Ignacio Matos
Alex Martínez
Rafael Morales
Eva Muñoz
Alejandro Navarro
Alba Noguerido
Maria Ochoa de Olza
Mafalda Oliveira
Nuria Pardo
Maria Coral Perez
Jordi Remon
Víctor Rodríguez
Enrique Sanz
Tamara Saurí
César Serrano
Cristina Suarez
Helena Verdaguer
Maria Vieito
Esther Zamora

SUMMARY

We focus on proof-of-concept and proof-of-mechanism trials with targeted therapies with special emphasis on cell signaling, cancer stem cells, and immuno-oncology. These include first-in-human studies of targeted therapies, rational combinations of targeted therapies, biomarker-driven trials, and studies in molecularly selected populations.

We link clinical research at the UITM with different areas of investigation carried out at VHIO, following a truly translational model. For selected projects, we match molecular biology and optimal tumor models with pharmacology and innovative clinical research by involving VHIO scientists in our trials (biomarker development, profound understanding of mechanisms of action and resistance).

We have collaborated with VHIO's Molecular Oncology and Cancer Genomics Groups, led by Paolo Nuciforo and Ana Vivancos respectively, to perform molecular analysis of patients' tumors. This enables us to select the optimal treatment for our patients with the experimental therapies available in our portfolio of clinical trials.

Importantly, in relation to precision oncology, VHIO is a founding member of both the WIN (Worldwide Innovative Networking in personalized cancer medicine), and the Cancer Core Europe Consortia. Both are non-governmental organizations that connect international (WIN) and/or European (CCE) cancer centers including VHIO to advance cancer diagnostics and therapeutics.

This year, our group and VHIO's Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, have led the design the Basket of Baskets (BoB) trial. This academic study and endorsed by Cancer Core Europe will integrate molecular prescreening, the development of new diagnostic tests such as circulating DNA, with the assessment of targeted therapies in populations of patients who, matched to specific molecular alterations, will be most likely to benefit from these treatments. The protocol of its first module, to be supported by a pharmaceutical company, was approved this year. It will be sent to the relevant authorities next year and first patient enrolment is envisaged towards the end of 2018.

We are expanding our expertise in immuno-oncology with a large portfolio of trials covering some of the most promising targets in immune checkpoints and cytokines. We are also converging immuno-oncology and genomics to further enhance and expand precision medicine against cancer, and initiating a working group focused on epigenetics.

Our Early Drug Development Group and the Phase I Unit (UITM) continue to establish VHIO as a leading reference in driving drug development and targeted therapies in oncology. Testament to this is the number of patients who entrust us with their care (445 patients enrolled in phase I and basket studies in 2017), the portfolio of different trials available (120 phase I trials and 17 basket studies in 2017), and the novelty of our programs in precision medicine and immunotherapy drug development. This is also evidenced by our leading role in Cancer Core Europe's Clinical Trials Task Force.

We have also fostered important alliances with the pharmaceutical industry (5 active and many more currently under evaluation), other clinical research organizations and academic centers of excellence, as well as several companies dedicated to advancing personalized cancer medicine and care.

STRATEGIC GOALS

  • Clinical early development of the best-in-class targeted therapies, determining the optimal schedule and patient population that would most likely benefit most from these drugs by participating in novel clinical trials.
  • Analyze patients' tumors for molecular aberrations that may predict the efficacy of targeted agents and enable a more precise selection of the most appropriate treatment matched to the specificities of individual patients with advanced cancer.
  • Link clinical research at the UITM with the various preclinical and translational research groups at VHIO, and foster powerful collaborations with different partners involved in drug development and translational research (phase I units, academic centers, consortia, pharmaceutical companies).

HIGHLIGHTS

  • As a leading institute in drug development at global level (PI3K/akt/mTOR inhibitors, MAPK, FGFR and MET inhibitors, or drugs targeting developmental pathways such as TGF-beta, SHH, WNT, and NOTCH), we clinically test the best in-class drugs. We have expanded our expertise to other cell-signaling pathway inhibitors such as immunotherapeutics including agents targeting PD1/PDL1, OX40, CD40, and engineered antibodies.
  • We have carried out many clinical trials with novel-novel combinations including the pairing of targeted therapies (novel/novel) and, in immuno-oncology, coupling checkpoint inhibitors with either chemotherapy, radiation (abscopal effect), targeted therapies, or other immunomodulatory agents (TGFbeta, LAG3, anti VEGFR2, CD40).
  • Performed several clinical trials with patients selected on molecular alterations: mutations in AKT1, EGFR, PIK3CA, PIK3CB, PTEN, IDH1, ALK, ROS1, BRAF, NRAS, KRAS, FGFR1 and 2, MET, HER2, HER3; amplifications in HER2, AKT 1, 2, and 3, FGFR1, MET, NOTCH1-4, rearrangements of NTRK1-3 ROS1, ALK, BRAF, RSPO2/3 and FGFR1-3, and alteration in protein expression of PTEN, or overexpression of PDL1, CEA and FAP.
  • Funding for a program to explore primary and acquired resistance to targeted therapies. This project integrates patient-derived xenografts and the analysis of next-generation sequencing of multiple tissue samples and circulating-free tumor DNA. In collaboration with VHIO's Ana Vivancos, Violeta Serra, Héctor G. Palmer and Joaquín Arribas, we are focusing on the fibroblast growth factor and the WNT pathway.
  • Co-development of molecular tests for patient screening (disease-oriented mutation panels for NGS platforms and Nanostring nCounter).
  • Funding for the first module of the Basket of Baskets (BoB) study, fully endorsed by the Cancer Core Europe Consortium, to assess the value of checkpoint inhibition in molecularly selected populations.
  • We also received funding to perform the 360º Resistance in ImmunoOncology Project (360RIO) for the evaluation of mechanisms of resistance to immune therapy. We perform NGS, RNA seq, TIL expansion and TC line establishment from tumor biopsies in patients receiving immune therapy.
  • 2017 launch of the VHIO-BBVA Foundation Comprehensive Program of Cancer Immunotherapy & Immunology in collaboration with Memorial Sloan Kettering Cancer Center.
  • VHIO received a Health Innovation Five ‘HI-5’ Award from the European Alliance for Personalised Medicine (EAPM) under the category of Best EU-based hospital for integrating personalised cancer medicine.

PI PAPER PICK (full list for 2017 below)

Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599.

Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829.

Hierro C, Alsina M, Sánchez M, Serra V, Rodon J, Tabernero J. Targeting the fibroblast growth factor receptor 2 in gastric cancer: promise or pitfall? Ann Oncol. 2017 Jun 1;28(6):1207-1216.

Martin- Liberal J, Ochoa de Olza M, Hierro C, Gros A, Rodon J, Tabernero J. The expanding role of immunotherapy. Cancer Treat Rev. 2017 Mar;54:74-86.

HORIZONS 2018

  • Expand our number of clinical trials adding new targeted therapies against novel promising targeted therapies and best-in-class therapies.
  • Increase our portfolio of molecular tests, adding new panels and tests to our program, and explore new platforms such as Oncoplex for proteomic profiling.
  • To continue to advance precision cancer medicine through the development of a second VHIO-led trial to explore personalized combinations of drugs through patient-derived primary cultures in order to predict drug sensitivity. In this regard, we will continue to seek additional funding for our Basket of Baskets project, endorsed by Cancer Core Europe.
  • To develop expertise in the emerging field of epigenetics and the signaling between tumor cells and the immune system as well as focus on early drug development of therapies that modulate that signaling through translational projects in immuno-oncology and epigenetics. We also aim to bridge the phase I program (and our strategic alliances with the pharmaceutical industry) with the expertise of two recently established VHIO groups: our Tumor Immunology and Immunotherapy Group led by Alena Gros , and the Chromatin Dynamics in Cancer Group headed by Sandra Peiró.
  • A training program for 3-4 oncologists in early drug development and translational research.

PUBLICATIONS

  1. Improving the armamentarium of PI3K inhibitors with isoform-selective agents: A new light in the darkness. Rodon J; Tabernero J. 2017.Cancer Discov.7: 666-669. IF:20,011
  2. Association of survival benefit with docetaxel in prostate cancer and total number of cycles administered: A post hoc analysis of the Mainsail study. de Morrée ES; Vogelzang NJ; Petrylak DP; Budnik N; Wiechno PJ; Sternberg CN; Doner K; Bellmunt J; Burke JM; Ochoa de Olza M; Choudhury A; Gschwend JE; Kopyltsov E; Flechon A; van As N; Houede N; Barton D; Fandi A; Jungnelius U; Li S; Li JS; de Wit R. 2017.JAMA Oncol.3: 68-75. IF:16,559
  3. Targeting the fibroblast growth factor receptor 2 in gastric cancer: Promise or pitfall?.Hierro C; Alsina M; Sánchez M; Serra V; Rodon J; Tabernero J. 2017.Ann Oncol.28: 1207-1216. IF:11,855
  4. The expanding role of immunotherapy.Martin-Liberal J; Ochoa de Olza M; Hierro C; Gros A; Rodon J; Tabernero J. 2017.Cancer Treat Rev.54: 74-86. IF:8,589
  5. Clinical research in small genomically stratified patient populations. Martin-Liberal J; Rodon J. 2017.Eur J Cancer.80: 73-82. IF:6,029
  6. First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours.Rodon J; Postel-Vinay S; Hollebecque A; Nuciforo P; Azaro A; Cattan V; Marfai L; Sudey I; Brendel K; Delmas A; Malasse S; Soria JC.2017.Eur J Cancer.81: 142-150. IF:6,029
  7. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification..Angevin E; Spitaleri G; Rodon J; Dotti K; Isambert N; Salvagni S; Moreno V; Assadourian S; Gomez C; Harnois M; Hollebecque A; Azaro A; Hervieu A; Rihawi K; De Marinis F. 2017.Eur J Cancer.87: 131-139. IF:6,029
  8. Weekly cabazitaxel plus prednisone is effective and less toxic for ‘unfit’ metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial. Climent MÁ; Pérez-Valderrama B; Mellado B; Fernández Parra EM; Fernández Calvo O; Ochoa de Olza M; Muinelo Romay L; Anido U; Domenech M; Hernando Polo S; Arranz Arija JÁ; Caballero C; Juan Fita MJ; Castellano D. 2017.Eur J Cancer.87: 30-37. IF:6,029
  9. Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights.Dienstmann R; Elez E; Argiles G; Matos I; Sanz-Garcia E; Ortiz C; Macarulla T; Capdevila J; Alsina M; Sauri T; Verdaguer H; Vilaro M; Ruiz-Pace F; Viaplana C; Garcia A; Landolfi S; Palmer HG; Nuciforo P; Rodon J; Vivancos A; Tabernero J. 2017.Mol Oncol.11: 1263-1272. IF:5,314
  10. Unveiling changes in the landscape of patient populations in cancer early drug development. Hierro C; Azaro A; Argilés G; Elez E; Gómez P; Carles J; Rodon J. 2017.Oncotarget.8: 14158-14172. IF:5,168
  11. Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab.Toledo RA; Cubillo A; Vega E; Garralda E; Alvarez R; de la Varga LU; Pascual JR; Sánchez G; Sarno F; Prieto SH; Perea S; Lopéz-Casas PP; López-Ríos F; Hidalgo M. 2017.Oncotarget.8: 35289-35300. IF:5,168
  12. Improving circulating tumor cells enumeration and characterization to predict outcome in first line chemotherapy mCRPC patients. León-Mateos L; Casas H; Abalo A; Vieito M; Abreu M; Anido U; Gómez-Tato A; López R; Abal M; Muinelo-Romay L. 2017.Oncotarget.8: 54708-54721. IF:5,168
  13. Novel combinations of PI3K-mTOR inhibitors with dacomitinib or chemotherapy in PTEN-deficient patient-derived tumor xenografts. Brana, Irene; Nhu-An Pham; Kim, Lucia; Sakashita, Shingo; Li, Ming; Ng, Christine; Wang, Yuhui; Loparco, Peter; Sierra, Rafael; Wang, Lisa; Clarke, Blaise A.; Neel, Benjamin G.; Siu, Lillian L.; Tsao, Ming-Sound. 2017.Oncotarget.8: 84659-84670. IF:5,168
  14. Development of Molecularly Driven Targeted Combination Strategies. Yap, Timothy A.; Rodon, Jordi. 2017.Oncologist.22: 1421-1423. IF:4,962
  15. Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).Capdevila J; Trigo JM; Aller J; Manzano JL; Garcia-Adrian S; Zafon C; Reig O; Bohn U; Ramon Y Cajal T; Duran M; Gonzalez-Astorga B; Lopez-Alfonso A; Medina J; Porras I; Reina JJ; Palacios N; Grande E; Cillan E; Matos I; Grau JJ. 2017.Eur J Endocrinol.177: 309-317. IF:4,101
  16. Immuno-Oncology: The Third Paradigm in Early Drug Development. Martin-Liberal J; Hierro C; Ochoa de Olza M; Rodon J. 2017.Target Oncol.12: 125-138. IF:3,438
  17. A Multi-Arm Phase I Study of the PI3K/mTOR Inhibitors PF-04691502 and Gedatolisib (PF-05212384) plus Irinotecan or the MEK Inhibitor PD-0325901 in Advanced Cancer. Wainberg ZA; Alsina M; Soares HP; Braña I; Britten CD; Del Conte G; Ezeh P; Houk B; Kern KA; Leong S; Pathan N; Pierce KJ; Siu LL; Vermette J; Tabernero J. 2017.Target Oncol.12: 775-785. IF:3,438
  18. The Treatment Landscape and New Opportunities of Molecular Targeted Therapies in Gastroenteropancreatic Neuroendocrine Tumors. Amair-Pinedo F; Matos I; Saurí T; Hernando J; Capdevila J. 2017.Target Oncol.12: 757-774. IF:3,438
  19. Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine..Capper D; von Deimling A; Brandes AA; Carpentier AF; Kesari S; Sepulveda-Sanchez JM; Wheeler HR; Chinot O; Cher L; Steinbach JP; Specenier P; Rodon J; Cleverly A; Smith C; Gueorguieva I; Miles C; Guba SC; Desaiah D; Estrem ST; Lahn MM; Wick W. 2017.INT J MOL SCI.. IF:3,226
  20. Epileptic features and survival in glioblastomas presenting with seizures. Toledo M; Sarria-Estrada S; Quintana M; Maldonado X; Martinez-Ricarte F; Rodon J; Auger C; Aizpurua M; Salas-Puig J; Santamarina E; Martinez-Saez E. 2017.EPILEPSY RES.130: 1-6. IF:2,367
  21. Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: A Spanish multicenter experience.Crespo G; Jiménez-Fonseca P; Custodio A; López C; Carmona-Bayonas A; Alonso V; Navarro M; Aller J; Sevilla I; Grande E; Gajate P; Alonso-Gordoa T; Matos I; Capdevila J; Nieto B; Barriuso J. 2017.FUTURE ONCOL.13: 615-624. IF:2,131
  22. Unraveling the hurdles in the development of HER2-targeted agents for metastatic gastro-esophageal cancer patients. Hierro, Cinta; Alsina, Maria; Tabernero, Josep. 2017.TRANSL CANCER RES.6: 1035-1039. IF:1,167

PROJECTS

  • 360 resistance: Matched therapies, resistance mechanisms and tumor heterogeneity.
  • Cellular Plasticity and Cancer.
  • Deciphering PI3K biology in health and disease.
  • Potenciación de la Citotoxicidad dependiente de Anticuerpo mediada por linfocitos NK para Inmunoterápia del cáncer.
  • Development of a systems biology method to predict efficacy of cancer drugs to optimize individualized therapeutics decision and improve clinical outcome for cancer patients (WINTHER).
  • Estudio de las alteraciones de FGFR como posible mecanismo de resistencia en pacientes que reciben tratamiento con pan-inhibidores de FGFR.
  • Basket of Baskets (BoB), from Cancer Core Europe.
  • MedBioinformatics.

Gastrointestinal & Endocrine Tumors Group

Imagen

Director
Josep Tabernero

Principal Investigator
Teresa Macarulla

Medical Oncologists and Clinical Fellows
Maria Alsina
Guillermo Argilés
Jaume Capdevila
Maria Elena Élez
Jorge Hernando
Ignacio Matos
Nuria Mulet
Alba Noguerido
Fabricio Eugenio Racca
Enrique Sanz
Tamara Saurí
Helena Verdaguer

Translational Investigator
Rodrigo A. Toledo

Clinical Nurse Specialist
Ariadna García

Masters Student
Giulia Martini

Bioinformatician
Pol Cusco

SUMMARY

In 2017, we have led and participated in several cooperative and singular research projects in gastrointestinal malignancies in addition to our key participation in existing international consortia of excellence including Cancer Core Europe, the WIN Consortium and EU FP7/H2020 supported studies.

Concerning the EU Horizon 2020 supported MoTricolor Consortium, coordinated by VHIO, I am pleased to report that the prescreening of patients commenced in 2017 and enrolment in the three clinical trials with different treatment strategies against the molecularly defined subtypes of colorectal cancer begins in 2018.

For the first time, patients will be stratified based on their gene expression profiles according to recently established predictive signatures, and we will seek to identify sensitivity of individual patients to the proposed experimental therapies. Additionally, comprehensive translational research will be performed using MoTriColor patients' samples through the INTRACOLOR project (supported by EU H2020's TRANSCAN-2 ERA NET), which is also coordinated by VHIO.

Reflected by publications in the most prestigious scientific titles in 2017, our group has also directed and collaborated in studies with important clinical implications, just some of which include:

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Bullman S et al. Science. 2017 Dec 15;358(6369):1443-1448.

This seminal study showed that the colonization of human colorectal cancer (CRC) with Fusobacterium and its associated microbiome is found in primary tumors and persists in liver metastases. Findings also revealed that it survives through the multiple generation of PDX and that treating mice bearing bacterium-positive models with metronidazole significantly decreases tumor growth.

These observations suggest that this bacterium is more than a mere bystander of tumorigenesis. It could in fact be a driver of metastases and selective antimicrobial therapy could therefore represent important weaponry for the treatment of patients with Fusobacterium-associated CRC.

HELOISE: Phase IIIb Randomized Multicenter Study Comparing Standard-of-Care and Higher-Dose Trastuzumab Regimens Combined With Chemotherapy as First-Line Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma. Shah MA et al. J Clin Oncol. 2017 Aug 1;35(22):2558-2567.

This multicenter and international study was designed to compare standard-of-care trastuzumab combined with chemotherapy with higher-dose trastuzumab plus chemotherapy. Co-authors assessed whether higher-dose trastuzumab increases trastuzumab serum trough concentration levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

Findings showed that increased trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals. HELOISE confirms standard-dose trastuzumab with chemotherapy as the standard of care for the first-line treatment of human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. Tejpar S et al. JAMA Oncol. 2017 3:194-201.

My third pick of our group's papers for 2017 is a study that was designed to evidence the prognostic and predictive value of primary tumor location in patients with RAS wild-type (RAS wt) metastatic colorectal cancer (mCRC) treated with first-line combination fluorouracil, leucovorin, and irinotecan (FOLFIRI) chemotherapy plus cetuximab in the Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL), and FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment For Patients With Metastatic Colorectal Cancer (FIRE-3) trials.

In the RAS wt populations of CRYSTAL and FIRE-3, patients with left-sided tumors had a markedly better prognosis than those with right-sided tumors. The pairing of First-line FOLFIRI with cetuximab showed clinical benefit in patients with left-sided tumors (vs FOLFIRI or FOLFIRI plus bevacizumab, respectively), while those patients with right-sided tumors derived limited benefit from standard therapies.

In our efforts to advance insights into the heterogeneity of metastatic colorectal cancer and better tackle the distinct molecular makeup of primary tumors arising from different regions of the colon, this study represents an important forward step by describing how primary tumor location impacts prognosis and response to therapy in patients with metastatic disease.

Effect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET-Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial. Shah MA et al. JAMA Oncol. 2017 May 1;3(5):620-627.

In the current era of precision medicine we must continue to assess and compare outcomes of novel combinations paired with standard treatments in our collective quest to improve response to therapy and halt metastatic spread. This collaborative phase III METGastric study assessed the combination of the MET inhibitor onartuzumab with standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced gastroesophageal adenocarcinoma (GEC), a tumor type with a typically poor prognosis.

Results revealed that the addition of onartuzumab to the mFOLFOX6 combination chemotherapy regimen, compared with mFOLFOX6 plus placebo, did not improve clinical benefit in the selected population. Subgroup analysis suggests non-Asian patients and patients without prior gastrectomy may stand to benefit. Additional studies may therefore establish the role of the MET pathway in GEC and thus ultimately represent an important forward step in improving outcomes for these patients.

A phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. Van Geel RM et al. 2017. Cancer Discov. 7: 610-619.

Speaking of combinations, results from this study, timed to coincide with the 2017 Annual Meeting of the American Association for Cancer Research (AACR), showed the promise of combining encorafenib with cetuximab, with or without alpelisib as a strategy against metastatic BRAF-mutant metastatic colorectal cancer (mCRC).

Both pairings demonstrated efficacy and acceptable safety profiles, with similar overall response rates: 19% in the dual and 18%in the triple combination group. In our efforts to suppress MAPK signalling and halt tumor growth in this difficult-to-treat population, these findings promise a new therapeutic avenue towards improving outcomes for patients.

As documented throughout this year's Report, 2017 has celebrated important updates concerning VHIO's various partnerships at national and international levels as well as the launch of new initiatives. To name but two:

Based on the successes marked to-date our CIBOT Program (Translational Biomedical and Oncological Research Consortium) supported by the pharmaceutical company Novartis has for the fourth time been renewed. Under the acronym SCITRON, this edition will focus on two subprojects:

Immunotherapy and early stage development: Translational study in patients accessing novel immunotherapy regimens at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”.

Colorectal cancer: Comprehensive genomic study in blood by liquid biopsy in samples from patients with this tumor type.

This agreement will certainly contribute to fortifying our determined efforts aimed at developing liquid biopsy as a clinically tried and tested approach for the more effective, less invasive ‘policing’ of cancer over time, in real time.

Additionally, as a direct reflection of our expertise in developing liquid biopsy at clinical level, driven in collaboration with our Cancer Genomics Group, VHIO counted two out of the five projects selected under the TRANSCAN Joint Translational Call on Minimally and non-invasive methods for early detection and/or progression of cancer.

Awarded by the Spanish Association against Cancer (AECC) and the Institute of Health Carlos III (ISCIII) through the ERA-NET TRANSCAN-2 program funded by EU's Horizon 2020, one of VHIO's two TRANSCANs focuses on the early detection of relapse in advanced colon cancer patients by longitudinally following a personalized molecular signature by liquid biopsy. This proof-of-concept, prospective and multi-center study seeks to evaluate the clinical feasibility of tracking tumor progression by dynamically detecting a molecular signature from a blood test. As an innovative approach for the early detection of disease relapse, this project represents an important next step in more accurately monitoring cancer's next moves.

STRATEGIC GOALS

  • Discovery and validation of novel biomarkers in gastrointestinal tumors.
  • Development of relevant preclinical models in vitro and in vivo with emphasis on the identification of predictive markers.
  • Molecular characterization of GI diseases: i.e. colorectal, gastric, pancreatic, biliary tract cancers. Study of targetable subtypes.
  • Early clinical research with innovative targets.
  • Clinical research in late stage with more translational endpoints, focusing on the identification of prognostic/ predictive biomarkers.
  • Design and leadership of investigator initiated trials (IIT), including Basket studies.
  • Participation in multidisciplinary/multinational consortia and collaborative research programs of excellence.
  • Validation of repurposed drugs or candidate drugs, in partnership with pharma companies or academic groups.
  • Expansion of our collaboration with other VHIO teams (Tumor Biomarkers, Cancer Genomics, and Stem Cells & Cancer Groups) and research institutions including the Catalan Institute of Oncology (ICO).
  • Expansion of research lines in GI cancers including the study of microbiota & immunology/immunotherapy.

HIGHLIGHTS

  • Early drug development and Phase I clinical trials in solid tumors with particular emphasis on developing molecular targeted therapies.
  • Molecular markers in gastrointestinal malignancies: we have significantly contributed to advancing insights into prognostic and predictive factors for response and efficacy with targeted agents across various gastrointestinal malignancies.
  • The design of investigator initiated trials as well as participation in several studies developed in collaboration with national and international cooperative groups (Sym004), as well as academic collaborative studies including research focused on Fusobacterium and colorectal cancer.
  • Participation in ongoing EU Horizon 2020-funded projects, MoTriColor and IntraColor, as Principal Investigators.
  • Our group is partner of many national and international consortia and networks including Cancer Core Europe, WIN and CIBERONC.

PI PAPER PICK (full list for 2017 below)

Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017 Dec 15;358(6369):1443-1448.

Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb Randomized Multicenter Study Comparing Standard-of-Care and Higher-Dose Trastuzumab Regimens Combined With Chemotherapy as First-Line Therapy in PatientsWith Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567.

Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, Bruey JM, Smith D, McCaffery I, Shames DS, Phan S, Cunningham D. Effect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET-Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial. JAMA Oncol. 2017 May 1;3(5):620-627.

Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-TypeMetastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 3:194-201.

HORIZONS 2018

  • Lead the design of/increased participation in novel Basket trials.
  • PIs of phase I and II studies with pharmacodynamic endpoints with novel agents directed to cancer and immune cells’ targets.
  • Continued (lead) participation in multidisciplinary/multinational consortia and collaborative research programs of excellence, as well as driving new partnerships through H2020-supported projects in particular.
  • Validation of repurposed drugs or candidate drugs, in partnership with pharma companies or academic groups.
  • Expansion of our collaboration with other VHIO teams (Tumor Biomarkers, Cancer Genomics, Molecular Oncology, and Stem Cells & Cancer Groups).

PUBLICATIONS

  1. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. Peters S; Camidge DR; Shaw AT; Gadgeel S; Ahn JS; Kim DW; Ou SI; Pérol M; Dziadziuszko R; Rosell R; Zeaiter A; Mitry E; Golding S; Balas B; Noe J; Morcos PN; Mok T; ALEX Trial Investigators. 2017.N Engl J Med.377: 829-838. IF:72,406
  2. CANCER A precision approach to tumour treatment. Dienstmann, Rodrigo; Tabernero, Josep. 2017.Nature.548: 40-41. IF:40,137
  3. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Zabala-Letona A; Arruabarrena-Aristorena A; Martín-Martín N; Fernandez-Ruiz S; Sutherland JD; Clasquin M; Tomas-Cortazar J; Jimenez J; Torres I; Quang P; Ximenez-Embun P; Bago R; Ugalde-Olano A; Loizaga-Iriarte A; Lacasa-Viscasillas I; Unda M; Torrano V; Cabrera D; van Liempd SM; Cendon Y; Castro E; Murray S; Revandkar A; Alimonti A; Zhang Y; Barnett A; Lein G; Pirman D; Cortazar AR; Arreal L; Prudkin L; Astobiza I; Valcarcel-Jimenez L; Zuñiga-García P; Fernandez-Dominguez I; Piva M; Caro-Maldonado A; Sánchez-Mosquera P; Castillo-Martín M; Serra V; Beraza N; Gentilella A; Thomas G; Azkargorta M; Elortza F; Farràs R; Olmos D; Efeyan A; Anguita J; Muñoz J; Falcón-Pérez JM; Barrio R; Macarulla T; Mato JM; Martinez-Chantar ML; Cordon-Cardo C; Aransay AM; Marks K; Baselga J; Tabernero J; Nuciforo P; Manning BD; Marjon K; Carracedo A. 2017.Nature.547: 109-0. IF:40,137
  4. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Bullman, Susan; Pedamallu, Chandra S.; Sicinska, Ewa; Claney, Thomas E.; Zhang, Xiaoyang; Cai, Diana; Neuberg, Donna; Huang, Katherine; Guevara, Fatima; Nelson, Timothy; Chipashvili, Otari; Hagan, Timothy; Walker, Mark; Ramachandran, Aruna; Diosdado, Begona; Serna, Garazi; Mulet, Nuria; Landolfi, Stefania; Ramon y Cajal, Santiago; Fasani, Roberta; Aguirre, Andrew J.; Ng, Kimmie; Elez, Elena; Ogino, Shuji; Tabernero, Josep; Fuchs, Charles S.; Hahn, William C.; Nuciforo, Paolo; Meyerson, Matthew. 2017.Science.358: 1443-0. IF:37,205
  5. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Dienstmann R; Vermeulen L; Guinney J; Kopetz S; Tejpar S; Tabernero J. 2017.Nat Rev Cancer.17: 79-92. IF:37,147
  6. The Cancer Moonshot from a European perspective.Ciardiello F; Tabernero J. 2017.Lancet Oncol.18: 626-0. IF:33,900
  7. Pembrolizumab in patients with extensive-stage small-cell lung cancer: Results from the phase Ib KEYNOTE-028 study.Ott, P.A.; Elez, E.; Hiret, S.; Kim, D.-W.; Morosky, A.; Saraf, S.; Piperdi, B.; Mehnert, J.M.. 2017.J Clin Oncol.35: 3823-3829. IF:24,008
  8. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1–positive endometrial cancer: Results from the KEYNOTE-028 study.Ott PA; Bang YJ; Berton-Rigaud D; Elez E; Pishvaian MJ; Rugo HS; Puzanov I; Mehnert JM; Aung KL; Lopez J; Carrigan M; Saraf S; Chen M; Soria JC. 2017.J Clin Oncol.35: 2535-2541. IF:24,008
  9. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2–positive metastatic gastric or gastroesophageal junction adenocarcinoma.Shah MA; Xu RH; Bang YJ; Hoff PM; Liu T; Herráez-Baranda LA; Xia F; Garg A; Shing M; Tabernero J. 2017.J Clin Oncol.35: 2558-2567. IF:24,008
  10. Targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges. Bradley CA; Salto-Tellez M; Laurent-Puig P; Bardelli A; Rolfo C; Tabernero J; Khawaja HA; Lawler M; Johnston PG; Van Schaeybroeck S; MErCuRIC consortium. 2017.Nat Rev Clin Oncol.14: 562-576. IF:20,693
  11. A first-in-human phase I study of the ATP-competitive AKT inhibitor Ipatasertib demonstrates Robust and safe targeting of AKT in patients with solid tumors. Saura C; Roda D; Roselló S; Oliveira M; Macarulla T; Pérez-Fidalgo JA; Morales-Barrera R; Sanchis-García JM; Musib L; Budha N; Zhu J; Nannini M; Chan WY; Sanabria Bohórquez SM; Meng RD; Lin K; Yan Y; Patel P; Baselga J; Tabernero J; Cervantes A. 2017.Cancer Discov.7: 102-113. IF:20,011
  12. A phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. van Geel RM; Tabernero J; Elez E; Bendell JC; Spreafico A; Schuler M; Yoshino T; Delord JP; Yamada Y; Lolkema M; Faris JE; Eskens FA; Sharma S; Yaeger R; Lenz HJ; Wainberg ZA; Avsar E; Chatterjee A; Jaeger S; Tan E; Maharry K; Demuth T; Schellens JH. 2017.Cancer Discov.7: 610-619. IF:20,011
  13. Improving the armamentarium of PI3K inhibitors with isoform-selective agents: A new light in the darkness.Rodon J; Tabernero J. 2017.Cancer Discov.7: 666-669. IF:20,011
  14. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer Retrospective Analyses of the CRYSTAL and FIRE-3 Trials.Tejpar, Sabine; Stintzing, Sebastian; Ciardiello, Fortunato; Tabernero, Josep; Van Cutsem, Eric; Beier, Frank; Esser, Regina; Lenz, Heinz-Josef; Heinemann, Volker. 2017.JAMA Oncol.3: 194-201. IF:16,559
  15. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: The METGastric randomized clinical trial.Shah MA; Bang YJ; Lordick F; Alsina M; Chen M; Hack SP; Bruey JM; Smith D; McCaffery I; Shames DS; Phan S; Cunningham D. 2017.JAMA Oncol.3: 620-627. IF:16,559
  16. Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer..Taieb J; Le Malicot K; Shi Q; Penault Lorca F; Bouché O; Tabernero J; Mini E; Goldberg RM; Folprecht G; Luc Van Laethem J; Sargent DJ; Alberts SR; Francois Emile J; Laurent Puig P; Sinicrope FA. 2017.J Natl Cancer Inst.IF:12,589
  17. Adherence to capecitabine in preoperative treatment of stage II and III rectal cancer: Do we need to worry?.Font R; Espinas JA; Layos L; Martinez Villacampa M; Capdevila J; Tobeña M; Pisa A; Pericay C; Lezcano C; Fort E; Cardona I; Berga N; Solà J; Borras JM. 2017.Ann Oncol.28: 831-835. IF:11,855
  18. Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients..Taieb J; Balogoun R; Le Malicot K; Tabernero J; Mini E; Folprecht G; Van Laethem JL; Emile JF; Mulot C; Fratté S; Levaché CB; Saban-Roche L; Thaler J; Petersen LN; Bridgewater J; Perkins G; Lepage C; Van Cutsem E; Zaanan A; Laurent-Puig P; for PETACC8 investigators. 2017.Ann Oncol.28: 824-830. IF:11,855
  19. Intratumoral heterogeneity in gastric cancer: a new challenge to face..Alsina M; Gullo I; Carneiro F. 2017.Ann Oncol.28: 912-913. IF:11,855
  20. A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial..Kulke MH; Ruszniewski P; Van Cutsem E; Lombard-Bohas C; Valle JW; De Herder WW; Pavel M; Degtyarev E; Brase JC; Bubuteishvili-Pacaud L; Voi M; Salazar R; Borbath I; Fazio N; Smith D; Capdevila J; Riechelmann RP; Yao JC. 2017.Ann Oncol.28: 1309-1315. IF:11,855
  21. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Grasselli J; Elez E; Caratù G; Matito J; Santos C; Macarulla T; Vidal J; Garcia M; Viéitez JM; Paéz D; Falcó E; Lopez Lopez C; Aranda E; Jones F; Sikri V; Nuciforo P; Fasani R; Tabernero J; Montagut C; Azuara D; Dienstmann R; Salazar R; Vivancos A. 2017.Ann Oncol.28: 1294-1301. IF:11,855
  22. Targeting the fibroblast growth factor receptor 2 in gastric cancer: Promise or pitfall? Hierro C; Alsina M; Sánchez M; Serra V; Rodon J; Tabernero J. 2017.Ann Oncol.28: 1207-1216. IF:11,855
  23. Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey. Banerjee S; Califano R; Corral J; de Azambuja E; De Mattos-Arruda L; Guarneri V; Hutka M; Jordan K; Martinelli E; Mountzios G; Ozturk MA; Petrova M; Postel-Vinay S; Preusser M; Qvortrup C; Volkov MNM; Tabernero J; Olmos D; Strijbos MH. 2017.Ann Oncol.28: 1590-1596. IF:11,855
  24. Reply to the letter to the editor 'Addressing the quality of the ESMO-MCBS' by Del Paggio. Cherny NI; Dafni U; Bogaerts J; Pentheroudakis G; Tabernero J; Zielinski C; de Vries EGE. 2017.Ann Oncol.28: 2031-2032. IF:11,855
  25. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Arnold D; Lueza B; Douillard JY; Peeters M; Lenz HJ; Venook A; Heinemann V; Van Cutsem E; Pignon JP; Tabernero J; Cervantes A; Ciardiello F. 2017.Ann Oncol.28: 1713-1729. IF:11,855
  26. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: Results from two randomized first-line panitumumab studies. Boeckx N; Koukakis R; Op de Beeck K; Rolfo C; Van Camp G; Siena S; Tabernero J; Douillard JY; André T; Peeters M. 2017.Ann Oncol.28: 1862-1868. IF:11,855
  27. Reply to the letter to the editor 'Can we trust burnout research?' by Bianchi et al. Banerjee S; Preusser M; Tabernero J; Strijbos M. 2017.Ann Oncol.28: 2625-2626. IF:11,855
  28. ESMO-Magnitude of Clinical Benefit Scale version 1.1.Cherny NI; Dafni U; Bogaerts J; Latino NJ; Pentheroudakis G; Douillard JY; Tabernero J; Zielinski C; Piccart MJ; de Vries EGE. 2017.Ann Oncol.28: 2340-2366. IF:11,855
  29. BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives. Sanz-Garcia E; Argiles G; Elez E; Tabernero J. 2017.Ann Oncol.28: 2648-2657. IF:11,855
  30. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Arnold D; Fuchs C; Tabernero J; Ohtsu A; Zhu AX; Garon EB; Mackey JR; Paz-Ares L; Baron AD; Okusaka T; Yoshino T; Yoon HH; Das M; Ferry D; Zhang Y; Lin Y; Binder P; Sashegyi A; Chau I. 2017.Ann Oncol.28: 2932-2942. IF:11,855
  31. DPYD genotype-guided fluoropyrimidines dose: is it ready for prime time? Páez D; Salazar R; Tabernero J. 2017.Ann Oncol.28: 2913-2914. IF:11,855
  32. A first-in-human, Phase I, dose-escalation study of TAK-117, A selective PI3Ka isoform inhibitor, in patients with advanced solid malignancies. Juric D; de Bono JS; LoRusso PM; Nemunaitis J; Heath EI; Kwak EL; Macarulla Mercadé T; Geuna E; Jose de Miguel-Luken M; Patel C; Kuida K; Sankoh S; Westin EH; Zohren F; Shou Y; Tabernero J. 2017.Clin Cancer Res.23: 5015-5023. IF:9,619
  33. Strategies to design clinical studies to identify predictive biomarkers in cancer research. Perez-Gracia JL; Sanmamed MF; Bosch A; Patiño-Garcia A; Schalper KA; Segura V; Bellmunt J; Tabernero J; Sweeney CJ; Choueiri TK; Martín M; Fusco JP; Rodriguez-Ruiz ME; Calvo A; Prior C; Paz-Ares L; Pio R; Gonzalez-Billalabeitia E; Gonzalez Hernandez A; Páez D; Piulats JM; Gurpide A; Andueza M; de Velasco G; Pazo R; Grande E; Nicolas P; Abad-Santos F; Garcia-Donas J; Castellano D; Pajares MJ; Suarez C; Colomer R; Montuenga LM; Melero I. 2017.Cancer Treat Rev.53: 79-97. IF:8,589
  34. The expanding role of immunotherapy. Martin-Liberal J; Ochoa de Olza M; Hierro C; Gros A; Rodon J; Tabernero J. 2017.Cancer Treat Rev.54: 74-86. IF:8,589
  35. Translational research in neuroendocrine tumors: Pitfalls and opportunities. Capdevila J; Casanovas O; Salazar R; Castellano D; Segura A; Fuster P; Aller J; García-Carbonero R; Jimenez-Fonseca P; Grande E; Castaño JP. 2017.Oncogene.36: 1899-1907. IF:7,519
  36. Pancreatic cancer heterogeneity and response to Mek inhibition. Pedersen K; Bilal F; Bernadó Morales C; Salcedo MT; Macarulla T; Massó-Vallés D; Mohan V; Vivancos A; Carreras MJ; Serres X; Abu-Suboh M; Balsells J; Allende E; Sagi I; Soucek L; Tabernero J; Arribas J. 2017.Oncogene.36: 5639-5647. IF:7,519
  37. Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial. Sclafani F; Kim TY; Cunningham D; Kim TW; Tabernero J; Schmoll HJ; Roh JK; Kim SY; Park YS; Guren TK; Hawkes E; Clarke SJ; Ferry D; Frodin JE; Ayers M; Nebozhyn M; Peckitt C; Loboda A; Watkins DJ. 2017.INT J CANCER.140: 431-439. IF:6,513
  38. Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer. Sclafani F; Brown G; Cunningham D; Wotherspoon A; Mendes LST; Balyasnikova S; Evans J; Peckitt C; Begum R; Tait D; Tabernero J; Glimelius B; Roselló S; Thomas J; Oates J; Chau I. 2017.Br J Cancer.117: 1478-1485. IF:6,176
  39. Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial. Yoshino T; Obermannová R; Bodoky G; Garcia-Carbonero R; Ciuleanu T; Portnoy DC; Kim TW; Hsu Y; Ferry D; Nasroulah F; Tabernero J. 2017.Eur J Cancer.78: 61-69. IF:6,029
  40. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX. Emile JF; Julié C; Le Malicot K; Lepage C; Tabernero J; Mini E; Folprecht G; Van Laethem JL; Dimet S; Boulagnon-Rombi C; Allard MA; Penault-Llorca F; Bennouna J; Laurent-Puig P; Taieb J; PETACC8 Study Investigators; Austrian Breast and Colorectal cancer Study Group (ABCSG); Belgian Group of Digestive Oncology (BGDO); Lone Nørgård Petersen; Fédération Francophone de Cancérologie Digestive (FFCD); Fédération Nationale des Centres de Lutte Contre le Cancer (UNICANCER); Fédération Nationale des Centres de Lutte Contre le Cancer Association Européenn; Arbeitsgemeinschaft Internistische Onkologie (AIO); Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD); Gruppo Oncologico dell'Italia Meridionale (GOIM); Istituto Oncologico Romagnolo (IOR); Gruppo Cooperativo Chirurgico Italiano (GOCCI); Gruppo Oncologico Nord Ovest (GONO); Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC); Gruppo Cooperativo do Cancro Digestivo da Associação Portuguesa de Investigação; Grupo Español para el Tratamiento de los Tumores Digestivos (TTD); John Allen Bridgewater. 2017.Eur J Cancer.82: 16-24. IF:6,029
  41. Optimization of RAS/BRAF mutational analysis confirms improvement in patient selection for clinical benefit to anti-EGFR treatment in metastatic colorectal cancer. Santos C; Azuara D; Garcia-Carbonero R; García Alfonso P; Carrato A; Elez E; Gómez A; Losa F; Montagut C; Massuti B; Navarro V; Varela M; López-Doriga A; Moreno V; Valladares M; Manzano JL; Viéitez JM; Aranda E; Sanjuan X; Tabernero J; Capella G; Salazar R. 2017.Mol Cancer Ther.16: 1999-2007. IF:5,764
  42. Exposure-response analyses of ramucirumab from two randomized, phase III trials of second-line treatment for advanced gastric or gastroesophageal junction cancer. Tabernero J; Ohtsu A; Muro K; Van Cutsem E; Oh SC; Bodoky G; Shimada Y; Hironaka S; Ajani JA; Tomasek J; Safran H; Chandrawansa K; Hsu Y; Heathman M; Khan A; Ni L; Melemed AS; Gao L; Ferry D; Fuchs CS. 2017.Mol Cancer Ther.16: 2215-2222. IF:5,764
  43. Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer. Jiménez-Fonseca P; Carmona-Bayonas A; Sánchez Lorenzo ML; Plazas JG; Custodio A; Hernández R; Garrido M; García T; Echavarría I; Cano JM; Rodríguez Palomo A; Mangas M; Macías Declara I; Ramchandani A; Visa L; Viudez A; Buxó E; Díaz-Serrano A; López C; Azkarate A; Longo F; Castañón E; Sánchez Bayona R; Pimentel P; Limón ML; Cerdá P; Álvarez Llosa R; Serrano R; Lobera MP; Alsina M; Hurtado Nuño A; Gómez-Martin C. 2017.Gastric Cancer.20: 465-474. IF:5,454
  44. Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights. Dienstmann R; Elez E; Argiles G; Matos I; Sanz-Garcia E; Ortiz C; Macarulla T; Capdevila J; Alsina M; Sauri T; Verdaguer H; Vilaro M; Ruiz-Pace F; Viaplana C; Garcia A; Landolfi S; Palmer HG; Nuciforo P; Rodon J; Vivancos A; Tabernero J. 2017.Mol Oncol.11: 1263-1272. IF:5,314
  45. Unveiling changes in the landscape of patient populations in cancer early drug development. Hierro C; Azaro A; Argilés G; Elez E; Gómez P; Carles J; Rodon J. 2017.Oncotarget.8: 14158-14172. IF:5,168
  46. Randomized phase II trial of parsatuzumab (Anti-EGFL7) or placebo in combination with FOLFOX and bevacizumab for first-line metastatic colorectal cancer. García-Carbonero R; van Cutsem E; Rivera F; Jassem J; Gore I; Tebbutt N; Braiteh F; Argiles G; Wainberg ZA; Funke R; Anderson M; McCall B; Stroh M; Wakshull E; Hegde P; Ye W; Chen D; Chang I; Rhee I; Hurwitz H. 2017.Oncologist.22: 375-30. IF:4,962
  47. Cell-Free DNA in metastatic colorectal cancer: A systematic review and Meta-Analysis. Spindler KG; Boysen AK; Pallisgård N; Johansen JS; Tabernero J; Sørensen MM; Jensen BV; Hansen TF; Sefrioui D; Andersen RF; Brandslund I; Jakobsen A. 2017.Oncologist.22: 1049-1055. IF:4,962
  48. A phase ib dose-escalation study of the safety, tolerability, and pharmacokinetics of cobimetinib and duligotuzumab in patients with previously treated locally advanced ormetastatic cancers with mutant KRAS. Lieu CH; Hidalgo M; Berlin JD; Ko AH; Cervantes A; LoRusso P; Gerber DE; Eder JP; Eckhardt SG; Kapp AV; Tsuhako A; McCall B; Pirzkall A; Uyei A; Tabernero J. 2017.Oncologist.22: 1024-89. IF:4,962
  49. Electronic tongues to assess wine sensory descriptors.Cetó X; González-Calabuig A; Crespo N; Pérez S; Capdevila J; Puig-Pujol A; Valle MD. 2017.Talanta.162: 218-224. IF:4,162
  50. Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).Capdevila J; Trigo JM; Aller J; Manzano JL; Garcia-Adrian S; Zafon C; Reig O; Bohn U; Ramon Y Cajal T; Duran M; Gonzalez-Astorga B; Lopez-Alfonso A; Medina J; Porras I; Reina JJ; Palacios N; Grande E; Cillan E; Matos I; Grau JJ. 2017.Eur J Endocrinol.177: 309-317. IF:4,101
  51. ENETS Consensus Recommendations for the Standards of Care in Neuroendocrine Neoplasms: Follow-Up and Documentation..Knigge U; Capdevila J; Bartsch DK; Baudin E; Falkerby J; Kianmanesh R; Kos-Kudla B; Niederle B; Nieveen van Dijkum E; O'Toole D; Pascher A; Reed N; Sundin A; Vullierme MP; all other Antibes Consensus Conference Participants. 2017.Neuroendocrinology.105: 310-319. IF:3,608
  52. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumours: Surgery for Small Intestinal and Pancreatic Neuroendocrine Tumours. Partelli S; Bartsch DK; Capdevila J; Chen J; Knigge U; Niederle B; Nieveen van Dijkum EJ; Pape UF; Pascher A; Ramage J; Reed N; Ruszniewski P; Scoazec JY; Toumpanakis C; Kianmanesh R; Falconi M; all other Antibes Consensus Conference participants. 2017.Neuroendocrinology.105: 255-265. IF:3,608
  53. Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C. Almhanna K; Miron ML; Wright D; Gracian AC; Hubner RA; Van Laethem JL; López CM; Alsina M; Muñoz FL; Bendell J; Firdaus I; Messersmith W; Ye Z; Fasanmade AA; Danaee H; Kalebic T. 2017.Invest New Drugs.35: 235-241. IF:3,484
  54. A Multi-Arm Phase I Study of the PI3K/mTOR Inhibitors PF-04691502 and Gedatolisib (PF-05212384) plus Irinotecan or the MEK Inhibitor PD-0325901 in Advanced Cancer. Wainberg ZA; Alsina M; Soares HP; Braña I; Britten CD; Del Conte G; Ezeh P; Houk B; Kern KA; Leong S; Pathan N; Pierce KJ; Siu LL; Vermette J; Tabernero J. 2017.Target Oncol.12: 775-785. IF:3,438
  55. The Treatment Landscape and New Opportunities of Molecular Targeted Therapies in Gastroenteropancreatic Neuroendocrine Tumors. Amair-Pinedo F; Matos I; Saurí T; Hernando J; Capdevila J. 2017.Target Oncol.12: 757-774. IF:3,438
  56. A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer. Reynolds KL; Bedard PL; Lee SH; Lin CC; Tabernero J; Alsina M; Cohen E; Baselga J; Blumenschein G; Graham DM; Garrido-Laguna I; Juric D; Sharma S; Salgia R; Seroutou A; Tian X; Fernandez R; Morozov A; Sheng Q; Ramkumar T; Zubel A; Bang YJ. 2017.BMC Cancer.17: 646-0. IF:3,288
  57. Genetics of Pheochromocytomas and Paragangliomas: An Overview on the Recently Implicated Genes MERTK, MET, Fibroblast Growth Factor Receptor 1, and H3F3A. Toledo RA. 2017.Endocrinol Metab Clin North Am.46: 459-489. IF:3,204
  58. Overexpression of Yes Associated Protein 1, an Independent Prognostic Marker in Patients with Pancreatic Ductal Adenocarcinoma, Correlated with Liver Metastasis and Poor Prognosis. Salcedo Allende MT; Zeron-Medina J; Hernandez J; Macarulla T; Balsells J; Merino X; Allende H; Tabernero J; Ramon Y Cajal Agüeras S. 2017.Pancreas.46: 913-920. IF:2,967
  59. Desmoid-Type Fibromatosis: Who, When, and How to Treat. Martínez Trufero J; Pajares Bernad I; Torres Ramón I; Hernando Cubero J; Pazo Cid R. 2017.Curr Treat Options Oncol.18: 29-0. IF:2,820
  60. Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. O’Neil, B.H.; Wallmark, J.M.; Lorente, D.; Elez, E.; Raimbourg, J.; Gomez-Roca, C.; Ejadi, S.; Piha-Paul, S.A.; Stein, M.N.; Abdul Razak, A.R.; Dotti, K.; Santoro, A.; Cohen, R.B.; Gould, M.; Saraf, S.; Stein, K.; Han, S.-W.. 2017.PLoS One.IF:2,806
  61. Exposure–response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.Cohn AL; Yoshino T; Heinemann V; Obermannova R; Bodoky G; Prausová J; Garcia-Carbonero R; Ciuleanu T; Garcia-Alfonso P; Portnoy DC; Van Cutsem E; Yamazaki K; Clingan PR; Polikoff J; Lonardi S; O'Brien LM; Gao L; Yang L; Ferry D; Nasroulah F; Tabernero J. 2017.Cancer Chemother Pharmacol.80: 599-608. IF:2,737
  62. Association of Performance Status and Pain in Metastatic Bone Pain Management in the Spanish Clinical Setting.Dómine Gómez, M.; Díaz Fernández, N.; Cantos Sánchez de Ibargüen, B.; Zugazabeitia Olabarría, L.; Martínez Lozano, J.; Poza de Celis, R.; Trujillo Vílchez, R.; Peláez Fernández, I.; Capdevila Castillón, J.; Traseira Lugilde, S.; Esteban González, E.. 2017.ADV THER.34: 136-147. IF:2,709
  63. Optimizing Somatostatin Analog Use in Well or Moderately Differentiated Gastroenteropancreatic Neuroendocrine Tumors..Carmona-Bayonas A; Jiménez-Fonseca P; Custodio A; Grande E; Capdevila J; López C; Teule A; Garcia-Carbonero R; Spanish Neuroendocrine Tumor Group (GETNE). 2017.CURR ONCOL REP.19: 72-0. IF:2,608
  64. Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma. Jiménez-Fonseca P; Gómez Saez JM; Santamaria Sandi J; Capdevila J; Navarro Gonzalez E; Zafon Llopis C; Ramón Y Cajal Asensio T; Riesco-Eizaguirre G; Grande E; Galofré JC. 2017.Clin Transl Oncol.19: 12-20. IF:2,353
  65. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial.Longo-Muñoz F; Argiles G; Tabernero J; Cervantes A; Gravalos C; Pericay C; Gil-Calle S; Mizuguchi H; Carrato-Mena A; Limón ML; Garcia-Carbonero R. 2017.Clin Transl Oncol.19: 227-235. IF:2,353
  66. Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI). Capdevila J; Galofré JC; Grande E; Zafón Llopis C; Ramón Y Cajal Asensio T; Navarro González E; Jiménez-Fonseca P; Santamaría Sandi J; Gómez Sáez JM; Riesco Eizaguirre G. 2017.Clin Transl Oncol.19: 279-287. IF:2,353
  67. Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain. Hidalgo M; Álvarez R; Gallego J; Guillén-Ponce C; Laquente B; Macarulla T; Muñoz A; Salgado M; Vera R; Adeva J; Alés I; Arévalo S; Blázquez J; Calsina A; Carmona A; de Madaria E; Díaz R; Díez L; Fernández T; de Paredes BG; Gallardo ME; González I; Hernando O; Jiménez P; López A; López C; López-Ríos F; Martín E; Martínez J; Martínez A; Montans J; Pazo R; Plaza JC; Peiró I; Reina JJ; Sanjuanbenito A; Yaya R; Carrato A. 2017.Clin Transl Oncol.19: 667-681. IF:2,353
  68. Adjuvant treatment for pancreatic ductal carcinoma.Macarulla T; Fernández T; Gallardo ME; Hernando O; López AM; Hidalgo M. 2017.Clin Transl Oncol.19: 1199-1204. IF:2,353
  69. Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: A Spanish multicenter experience. Crespo G; Jiménez-Fonseca P; Custodio A; López C; Carmona-Bayonas A; Alonso V; Navarro M; Aller J; Sevilla I; Grande E; Gajate P; Alonso-Gordoa T; Matos I; Capdevila J; Nieto B; Barriuso J. 2017.FUTURE ONCOL.13: 615-624. IF:2,131
  70. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial. Tabernero J; Kunzmann V; Scheithauer W; Reni M; Shiansong Li J; Ferrara S; Djazouli K. 2017.Onco Targets Ther.10: 591-596. IF:1,653
  71. Unraveling the hurdles in the development of HER2-targeted agents for metastatic gastro-esophageal cancer patients.Hierro, Cinta; Alsina, Maria; Tabernero, Josep. 2017.TRANSL CANCER RES.6: 1035-1039. IF:1,167
  72. Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology. Garralda E; Dienstmann R; Tabernero J. 2017.Am Soc Clin Oncol Educ Book.37: 210-215.
  73. The European Cancer Patient's Bill of Rights, update and implementation 2016. Højgaard L; Löwenberg B; Selby P; Lawler M; Banks I; Law K; Albreht T; Armand JP; Barbacid M; Barzach M; Bergh J; Cameron D; Conte P; de Braud F; de Gramont A; De Lorenzo F; Diehl V; Diler S; Erdem S; Geissler J; Gore-Booth J; Henning G; Horgan D; Jassem J; Johnson P; Kaasa S; Kapitein P; Karjalainen S; Kelly J; Kienesberger A; La Vecchia C; Lacombe D; Lindahl T; Luzzatto L; Malby R; Mastris K; Meunier F; Murphy M; Naredi P; Nurse P; Oliver K; Pearce J; Pelouchov J; Piccart M; Pinedo B; Spurrier-Bernard G; Sullivan R; Tabernero J; Van de Velde C; van Herk B; Vedsted P; Waldmann A; Weller D; Wilking N; Wilson R; Yared W; Zielinski C; Zur Hausen H; Le Chevalier T; Johnston P. 2017.ESMO Open.
  74. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. Tabernero J; Vyas M; Giuliani R; Arnold D; Cardoso F; Casali PG; Cervantes A; Eggermont AM; Eniu A; Jassem J; Pentheroudakis G; Peters S; Rauh S; Zielinski CC; Stahel RA; Voest E; Douillard JY; McGregor K; Ciardiello F. 2017.ESMO Open.
  75. Radiological imaging markers predicting clinical outcome in patients with metastatic colorectal carcinoma treated with regorafenib: post hoc analysis of the CORRECT phase III trial (RadioCORRECT study)..Ricotta R; Verrioli A; Ghezzi S; Porcu L; Grothey A; Falcone A; Van Cutsem E; Argilés G; Adenis A; Ychou M; Barone C; Bouché O; Peeters M; Humblet Y; Mineur L; Sobrero AF; Hubbard JM; Cremolini C; Prenen H; Tabernero J; Jarraya H; Mazard T; Deguelte-Lardiere S; Papadimitriou K; Van den Eynde M; Pastorino A; Redaelli D; Bencardino K; Funaioli C; Amatu A; Carlo-Stella G; Torri V; Sartore-Bianchi A; Vanzulli A; Siena S. 2017.ESMO Open.
  76. Predictive and prognostic biomarkers in personalized gastrointestinal cancer treatment.Verdaguer H; Saurí T; Macarulla T. 2017.J Gastrointest Oncol.8: 405-417.
  77. The Role of Fluoropirimidines in Gastrointestinal Tumours: from the Bench to the Bed. Hernando-Cubero J; Matos-García I; Alonso-Orduña V; Capdevila J. 2017.J Gastrointest Cancer.48: 135-147.
  78. Towards shedding some light on regorafenib treatment in refractory metastatic colorectal cancer. Prager, Gerald; Argiles, Guillem. 2017.ESMO Open.
  79. Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules. Dafni U; Karlis D; Pedeli X; Bogaerts J; Pentheroudakis G; Tabernero J; Zielinski CC; Piccart MJ; de Vries EGE; Latino NJ; Douillard JY; Cherny NI. 2017.ESMO Open.
  80. Proxies of quality of life in metastatic colorectal cancer: analyses in the RECOURSE trial. Van Cutsem E; Falcone A; Garcia-Carbonero R; Komatsu Y; Pastorino A; Peeters M; Shimada Y; Yamazaki K; Yoshino T; Zaniboni A; Amellal N; Kanehisa A; Winkler R; Makris L; Mayer RJ; Ohtsu A; Tabernero J. 2017.ESMO Open.
  81. QTWiST analysis of the RECOURSE trial of trifluridine/tipiracil in metastatic colorectal cancer. Tabernero J; Van Cutsem E; Ohtsu A; Amellal N; Cadour S; Fougeray R; Haffemayer B; Mayer RJ. 2017.ESMO Open.

Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group

Imagen

Principal Investigator
Joan Carles

Medical Oncologists and Clinical Fellows
Rafael Morales
Fabricio Eugenio Racca
Jordi Rodón
César Serrano
Cristina Suarez
Claudia Valverde

SUMMARY

Our group is dedicated to both clinical and translational research, and has broad experience and grounded expertise in the treatment of various neoplasms. We design and develop clinical trials for genitourinary malignancies at different stages of disease in collaboration with urologists and radiation therapists. During 2017 we set up our Prostate Task Force. By closely connecting clinical and translational researchers at VHIO and the Vall d'Hebron Research Institute (VHIR), we are now initiating translational projects focused on these tumors. We will aim to extend our efforts to other malignancies studied by our group.

Over recent years, many developments have been reported in GU malignancies; in prostate, bladder, and kidney cancer in particular. Immunotherapy is proving increasingly important in the treatment of bladder and kidney cancer, and in 2017 we observed that it could also be important in the treatment of certain subgroups of patients with castration-resistant prostate cancer. Our group has participated in various clinical trials using checkpoint inhibitors that have changed the standard treatment for second line metastatic bladder cancer and first line metastatic kidney cancer. Close connectivity with all specialists involved in the treatment of these tumors is consequently paramount.

We also continue to develop our translational research platform for urologic cancer, as well as conduct clinical trials in early, adjuvant as well as metastatic disease. Our group collaborates with other research centers of excellence including the Cleveland Clinic (Ohio, USA), University of California, San Francisco (California, USA). We also work on clinical studies carried out in partnership with the Gustave Roussy Institute (Paris, France), Barts Hospital (London, UK), Kantonsspital St. Gallen (Switzerland), as well as the Biomedical Research Institute of Bellvitge - IDIBELL (Barcelona, Spain).

Throughout 2017, we have consolidated our translational research program with the establishment of a new research group at VHIO. Our Prostate Cancer Translational Research Group (click here), led by Principal Investigator Joaquin Mateo (MD trained at the in the Institute of Cancer Research – Royal Marsden NHS Foundation Trust, London, UK), will focus on metastatic castration-resistant prostate cancer.

His group will aim to refine a predictive biomarker suite for DNA repair targeting agents in metastatic prostate cancer. Research will center on how AR and TP53 status modulate the functional impact of DNA repair gene mutations, and how these factors determine tumor drug sensitivity. Joaquin will also establish a platform for systematic metastatic tissue acquisition from prostate cancer patients at VHIO.

We have also expanded our avatar program for kidney cancer tumors in collaboration with IDIBELL and have now implanted more than 25 samples. Additionally, we are partner of REVOLUTION: pREdiction of niVOLUmab acTION metastatic renal cancer patients:Treg function, tumoral access and NK interactions as predictive biomarkers of immunotherapy, funded by TRANSCAN-2 ERA-NET, under the EU framework programme Horizon 2020.

In addition, our group develops several multidisciplinary clinical studies and phase I trials in CNS tumors, in close connectivity with other professionals in neurosurgery and radiation therapy.

In collaboration with VHIO's Gene Expression & Cancer Group led by Joan Seoane, Director of Translational Research at our Institute, we are expanding our translational research platform for glioblastoma. We are working with different centers across Europe to develop a vaccine for patients with glioblastoma, and are now initiating the Phase I program. This project is supported by the European Commission's 7th Framework Programme of Research and Development. We also received a national grant to analyze cfDNA in blood and cephaloraquidic liquid for the analysis of primary CNS tumors and metastases.

We also work closely with the Spanish Sarcoma Group (GEIS) to conduct clinical trials at different stages of disease with emphasis on a histology-tailored design and are currently setting up a translational platform for sarcomas and basic research in partnership with IDIBELL and the Cancer Research Center of Salamanca - CIC (Spain). For GIST tumors we are working with J. Fletcher's lab at the Brigham and Women's Hospital (Boston, USA). One of our group members, César Serrano, who carried out a three-year fellowship at the Dana Farber Cancer Institute (Boston), has established an independent line of experimental research focused on sarcomas. Importantly, his translational studies have led to new treatment strategies in sarcoma, including the design of a phase Ib clinical trial to assess, for the first time in oncology, a rapid-alternation drug schedule of targeted therapies (NCT02164240). We are also currently developing novel strategies in GIST therapy in partnership with other referral centers across Europe and pharmaceutical companies.

Our Serum Bank now includes the majority of our tumor types (CNS tumors, GIST; renal cell carcinoma and CRPC), and we will continue to recruit samples from our patients. Dedicated to promoting education and exchange, in 2017 we welcomed five fellows from in and outside of Spain for three-month short stay visits.

STRATEGIC GOALS

  • Design and develop clinical trials covering all malignancies studied by our group. We strive to provide our patients with the most novel and optimal treatments including immune-based therapeutics, targeted therapies and new chemotherapies.
  • Conduct clinical trials at different stages of disease with emphasis on a histology-tailored design and multidisciplinary approach.
  • Develop new approaches including liquid biopsies for our patients in order to more precisely tailor treatments against CRPC, GIST and kidney cancer.
  • Consolidate our biopsy program (mainly in bone), for patients with CRPC to target main genomic alterations including PI3K pathways, DNA repair genes, and androgen receptor alterations.
  • Further consolidate our Prostate Cancer Task Force at VHIO and the Vall d'Hebron Research Institute (VHIR).
  • Expand our translational research platform for glioblastoma in collaboration with VHIO's Gene Expression & Cancer Group.
  • Create a translational platform for kidney cancer and sarcomas and basic research in partnership with the Biomedical Research Institute of Bellvitge (IDIBELL).
  • Set up a translational platform for GIST and expand research in collaboration with the Spanish Sarcoma Group (GEIS), and other European referral centers.

HIGHLIGHTS

  • New cancer medicines against GU malignancies: we have participated in important trials with different drugs (ODM 201; combination of abiraterone acetate with or without radium 223, PARP inhibitors), that have shown promise in improving outcomes for patients with prostate cancer. We are also participating in pioneering clinical studies with BET inhibitors and immune checkpoint inhibitors.
  • Other GU malignancies (renal and bladder): we are involved in clinical trials to evidence the utility of novel agents in modulating the host immune response against cancer (PD-1 and PDL-1) in first and second line treatment. These agents may be administered alone or in combination with other targeted therapies or chemotherapeutics.
  • Central Nervous System (CNS) tumors: research has expanded with the development of additional clinical trials and the creation of a tumor board comprised of experts in neurosurgery, radiology, radiotherapy, translational research, and medical oncology.
  • Sarcoma: we are developing new therapies for liposarcomas (mdm2 inhibitors), and GIST.

PI PAPER PICK (full list for 2017 below)

Eisenberger M, Hardy-Bessard AC, Kim CS, Géczi L, Ford D, Mourey L, Carles J, Parente P, Font A, Kacso G, Chadjaa M, Zhang W, Bernard J, de Bono J. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206.

García-Donas J, Font A, Pérez-Valderrama B, Virizuela JA, Climent MÁ, Hernando-Polo S, Arranz JÁ, Del Mar Llorente M, Lainez N, Villa-Guzmán JC, Mellado B, Del Alba AG, Castellano D, Gallardo E, Anido U, Del Muro XG, Domènech M, Puente J, Morales-Barrera R, Pérez-Gracia JL, Bellmunt J. Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial. Lancet Oncol. 2017 May;18(5):672-681.

Necchi A, Sonpavde G, Lo Vullo S, Giardiello D, Bamias A, Crabb SJ, Harshman LC, Bellmunt J, De Giorgi U, Sternberg CN, Cerbone L, Ladoire S, Wong YN, Yu EY, Chowdhury S, Niegisch G, Srinivas S, Vaishampayan UN, Pal SK, Agarwal N, Alva A, Baniel J, Golshayan AR, Morales-Barrera R, Bowles DW, Milowsky MI, Theodore C, Berthold DR, Daugaard G, Sridhar SS, Powles T, Rosenberg JE, Galsky MD, Mariani L; RISC Investigators. Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy: Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC). Eur Urol. 2017 Feb;71(2):281-289.

Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discov. 2017 Jan;7(1):102-113.

HORIZONS 2018

In 2018 we aim to consolidate our clinical and translational research in the castration-resistant prostate cancer (CRPC) and sarcoma fields, and advance progress in the treatment of GIST. We will also seek to accelerate tailored treatments in GU malignancies and CNS tumors through our translational research:

  • In prostate cancer: through our new group led by Joaquin Mateo at VHIO we will strive to reinforce biomarker refinements for DNA repair aberrations and establish a program for precision medicine in clinical practice. All the biopsies will be bone/ visceral-based liquid biopsy and we will also study germline mutations in saliva. Our group will also carry out innovative clinical trials with special focus on new drugs related to DNA damage. We will consolidate a serum bank for all patients with CRPC and develop novel tools (Beaming) in order to select more precise treatments for our patients.
  • In renal cell we will continue to foster a close relationship with the Cleveland Clinic (Ohio, USA), and start working on developing new biomarkers in partnership with other hospitals across Spain. In renal cell carcinoma we are also implementing the Avatar program and plan to apply the same strategy to other high risk subpopulations of GU tumors.
  • We will develop new therapies in CNS according to the mouse model developed by VHIO´s Gene Expression and Cancer Group led by Joan Seoane, mainly related to PI3K and TGF beta inhibitors. In addition, we will correlate these data with circulating DNA from patients with CNS tumors and brain metastases.

We hope to further increase our participation in Phase I trials carried out at the Research Unit for Molecular Therapy of Cancer UITM - "la Caixa". These superb facilities enable novel studies on innovative drugs and therapeutic leads to both potentiate pharmacological therapies against cancer and reduce their toxicity.

PUBLICATIONS

  1. Slovin S, Clark W, Carles J , Krivoshik A, Park JW, Wang F, George D. Seizure Rates in Enzalutamide-Treated Men With Metastatic Castration-Resistant Prostate Cancer and Risk of Seizure: The UPWARD Study. JAMA Oncol. 2017 Dec 7. doi: 10.1001/jamaoncol.2017.3361. [Epub ahead of print]
  2. Perez-Gracia JL, Loriot Y, Rosenberg JE, Powles T, Necchi A, Hussain SA, Morales-Barrera R, Retz MM, Niegisch G, Durán I, Théodore C, Grande E, Shen X, Wang J, Nelson B, Derleth CL, van der Heijden MS.  Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens.  Eur Urol. 2017 Dec 19. pii: S0302-2838(17)31015-1. doi: 10.1016/j.eururo.2017.11.023. [Epub ahead of print]
  3. Morote J, Comas I, Planas J, Maldonado X, Celma A, Placer J, Ferrer R, Carles J, Regis L. Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy. Clin Genitourin Cancer. 2017 Nov 30. pii: S1558-7673(17)30341-5. doi: 10.1016/j.clgc.2017.10.025. [Epub ahead of print]
  4. Rodriguez-Vida A, Torregrosa MD, Pinto Á, Climent MÁ, Olmos D, Carles J . Selection and monitoring of patients with metastatic castration-resistant prostate cancer for treatment with radium-223. Clin Transl Oncol. 2017 Nov 2. doi: 10.1007/s12094-017-1785-0. [Epub ahead of print] Review.
  5. Gallardo E, Méndez-Vidal MJ, Pérez-Gracia JL, Sepúlveda-Sánchez JM, Campayo M, Chirivella-González I, García-Del-Muro X, González-Del-Alba A, Grande E, Suárez C. SEOM clinical guideline for treatment of kidney cancer (2017). Clin Transl Oncol. 2017 Nov 13. doi: 10.1007/s12094-017-1765-4. [Epub ahead of print]
  6. Calvo E, Azaro A, Rodon J, Dirix L, Huizing M, Senecal FM, LoRusso P, Yee L, Poggesi I, de Jong J, Triantos S, Park YC, Knoblauch RE, Parekh TV, Demetri GD, von Mehren M. Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial.Invest New Drugs. 2017 Nov 27. doi: 10.1007/s10637-017-0546-9. [Epub ahead of print]
  7. Miller K, Carles J, Gschwend JE, Van Poppel H, Diels J, Brookman-May SD. The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score. Eur Urol. 2017 Sep 20. pii: S0302-2838(17)30728-5. doi: 10.1016/j.eururo.2017.08.035. [Epub ahead of print]
  8. Ryan CJ, Kheoh T, Li J, Molina A, De Porre P, Carles J, Efstathiou E, Kantoff PW, Mulders PFA, Saad F, Chi KN. Prognostic Index Model for Progression-Free Survival in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Plus Prednisone. Clin Genitourin Cancer. 2017 Jul 25. pii: S1558-7673(17)30211-2. doi: 10.1016/j.clgc.2017.07.014. [Epub ahead of print]
  9. Necchi A, Pond GR, Smaldone MC, Pal SK, Chan K, Wong YN, Viterbo R, Sonpavde G, Harshman LC, Crabb S, Alva A, Chowdhury S, De Giorgi U, Srinivas S, Agarwal N, Bamias A, Baniel J, Golshayan AR, Ladoire S, Sternberg CN, Cerbone L, Yu EY, Bellmunt J, Vaishampayan U, Niegisch G, Hussain S, Bowles DW, Morales-Barrera R, Milowsky MI, Theodore C, Berthold DR, Sridhar SS, Powles T, Rosenberg JE, Galsky MD; Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC). Robot-assisted Versus Open Radical Cystectomy in Patients Receiving Perioperative Chemotherapy for Muscle-invasive Bladder Cancer: The Oncologist's Perspective from a Multicentre Study. Eur Urol Focus. 2017 Mar 31. pii: S2405-4569(17)30079-2. doi: 10.1016/j.euf.2017.03.011. [Epub ahead of print]
  10. Martin-Broto J, Redondo A, Valverde C, Vaz MA, Mora J, Garcia Del Muro X, Gutierrez A, Tous C, Carnero A, Marcilla D, Carranza A, Sancho P, Martinez-Trufero J, Diaz-Beveridge R, Cruz J, Encinas V, Taron M, Moura DS, Luna P, Hindi N, Lopez-Pousa A. Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS). Ann Oncol. 2017 Dec 1;28(12):2994-2999
  11. Redondo A, Bagué S, Bernabeu D, Ortiz-Cruz E, Valverde C, Alvarez R, Martinez-Trufero J, Lopez-Martin JA, Correa R, Cruz J, Lopez-Pousa A, Santos A, García Del Muro X, Martin-Broto J. Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS). Cancer Chemother Pharmacol. 2017 Dec;80(6):1113-1131
  12. Alumkal JJ, Chowdhury S, Loriot Y, Sternberg CN, de Bono JS, Tombal B, Carles J, Flaig TW, Dorff TB, Phung, Forer D, Noonberg SB, Mansbach H, Beer TM, Higano CS. Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial. Clin Genitourin Cancer. 2017 Oct;15(5):610-617.e3.
  13. Eisenberger M, Hardy-Bessard AC, Kim CS, Géczi L, Ford D, Mourey L, Carles J, Parente P, Font A, Kacso G, Chadjaa M, Zhang W, Bernard J, de Bono J. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206.
  14. Joensuu H, Blay JY, Comandone A, Martin-Broto J, Fumagalli E, Grignani G, Del Muro XG, Adenis A, Valverde C, Pousa AL, Bouché O, Italiano A, Bauer S, Barone C, Weiss C, Crippa S, Camozzi M, Castellana R, Le Cesne A. Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib. Br J Cancer. 2017 Oct 24;117(9):1278-1285
  15. Mora J, Castañeda A, Perez-Jaume S, Lopez-Pousa A, Maradiegue E, Valverde C, Martin-Broto J, Garcia Del Muro X, Cruz O, Cruz J, Martinez-Trufero J, Maurel J, Vaz MA, de Alava E, de Torres C. GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS). Br J Cancer. 2017 Sep 5;117(6):767-774.
  16. Salah S, Lee JL, Rozzi A, Kitamura H, Matsumoto K, Vis DJ, Srinivas S, Morales-Barrera R, Carles J, Al-Rimawi D, Lee S, Kim KH, Izumi K, Lewin J. Second-line Chemotherapy in Older Patients With Metastatic Urothelial Carcinoma: Pooled Analysis of 10 Second-line Studies. Clin Genitourin Cancer. 2017 Aug;15(4):e563-e571.
  17. Bellmunt J, Kerst JM, Vázquez F, Morales-Barrera R, Grande E, Medina A, González Graguera MB, Rubio G, Anido U, Fernández Calvo O, González-Billalabeitia E, Van den Eertwegh AJM, Pujol E, Perez-Gracia JL, González Larriba JL, Collado R, Los M, Maciá S, De Wit R; SOGUG and DUOS. A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN). Ann Oncol. 2017 Jul 1;28(7):1517-1522
  18. Serrano C, George S, Valverde C, Olivares D, García-Valverde A, Suárez C, Morales-Barrera R, Carles J. Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors. Target Oncol. 2017 Jun;12(3):277-288.
  19. García-Donas J, Font A, Pérez-Valderrama B, Virizuela JA, Climent MÁ, Hernando-Polo S, Arranz JÁ, Del Mar Llorente M, Lainez N, Villa-Guzmán JC, Mellado B, Del Alba AG, Castellano D, Gallardo E, Anido U, Del Muro XG, Domènech M, Puente J, Morales-Barrera R, Pérez-Gracia JL, Bellmunt J.  Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial. Lancet Oncol. 2017 May;18(5):672-681.
  20. González Del Alba A, Arranz JÁ, Puente J, Méndez-Vidal MJ, Gallardo E, Grande E, Pérez-Valderrama B, González-Billalabeitia E, Lázaro-Quintela M, Pinto Á, Lainez N, Piulats JM, Esteban E, Maroto Rey JP, García JA, Suárez C.Recent advances in genitourinary tumors: A review focused on biology and systemic treatment. Crit Rev Oncol Hematol. 2017 May;113:171-190.
  21. Puente J, Laínez N, Dueñas M, Méndez-Vidal MJ, Esteban E, Castellano D, Martinez-Fernández M, Basterretxea L, Juan-Fita MJ, Antón L, León L, Lambea J, Pérez-Valderrama B, Vázquez S, Suarez C, Del Muro XG, Gallardo E, Maroto JP, Samaniego ML, Suárez-Paniagua B, Sanz J, Paramio JM; SOGUG (Spanish Oncology Genitourinary Group). Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma. Oncotarget. 2017 May 2;8(18):30410-30421
  22. Martin-Broto J, Martinez-Marín V, Serrano C, Hindi N, López-Guerrero JA, Ramos-Asensio R, Vallejo-Benítez A, Marcilla-Plaza D, González-Cámpora R. Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis.Clin Transl Oncol. 2017 May;19(5):536-545.
  23. Capper D, von Deimling A, Brandes AA, Carpentier AF, Kesari S, Sepulveda-Sanchez JM, Wheeler HR, Chinot O, Cher L, Steinbach JP, Specenier P, Rodon J, Cleverly A, Smith C, Gueorguieva I, Miles C, Guba SC, Desaiah D, Estrem ST, Lahn MM, Wick W.  Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine. Int J Mol Sci. 2017 May 6;18(5)
  24. Poveda A, García Del Muro X, López-Guerrero JA, Cubedo R, Martínez V, Romero I, Serrano C, Valverde C,Martín-Broto J; GEIS (Grupo Español de Investigación en Sarcomas/Spanish Group for Sarcoma Research). GEIS guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev. 2017 Apr;55:107-119.
  25. Hierro C, Azaro A, Argilés G, Elez E, Gómez P, Carles J, Rodon J. Unveiling changes in the landscape of patient populations in cancer early drug development. Oncotarget. 2017 Feb 21;8(8):14158-14172. Review
  26. Necchi A, Sonpavde G, Lo Vullo S, Giardiello D, Bamias A, Crabb SJ, Harshman LC, Bellmunt J, De Giorgi U, Sternberg CN, Cerbone L, Ladoire S, Wong YN, Yu EY, Chowdhury S, Niegisch G, Srinivas S, Vaishampayan UN, Pal SK, Agarwal N, Alva A, Baniel J, Golshayan AR, Morales-Barrera R, Bowles DW, Milowsky MI, Theodore C, Berthold DR, Daugaard G, Sridhar SS, Powles T, Rosenberg JE, Galsky MD, Mariani L; RISC Investigators. Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy: Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC). Eur Urol. 2017 Feb;71(2):281-289.
  27. Perez-Gracia JL, Sanmamed MF, Bosch A, Patiño-Garcia A, Schalper KA, Segura V, Bellmunt J, Tabernero J, Sweeney CJ, Choueiri TK, Martín M, Fusco JP, Rodriguez-Ruiz ME, Calvo A, Prior C, Paz-Ares L, Pio R, Gonzalez-Billalabeitia E, Gonzalez Hernandez A, Páez D, Piulats JM, Gurpide A, Andueza M, de Velasco G, Pazo R, Grande E, Nicolas P, Abad-Santos F, Garcia-Donas J, Castellano D, Pajares MJ, Suarez C, Colomer R, Montuenga LM, Melero I. Strategies to design clinical studies to identify predictive biomarkers in cancer research.Cancer Treat Rev. 2017 Feb;53:79-97
  28. Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martinez-Ricarte F, Rodon J, Auger C, Aizpurua M, Salas-Puig J, Santamarina E, Martinez-Saez E. Epileptic features and survival in glioblastomas presenting with seizures. Epilepsy Res. 2017 Feb;130:1-6.
  29. Regis L, Planas J, Carles J, Maldonado X, Comas I, Ferrer R, Morote J. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone. Prostate. 2017 Jan;77(1):114-120.
  30. Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discov. 2017 Jan;7(1):102-113.
  31. Cebrián A, Gómez Del Pulgar T, Méndez-Vidal MJ, Gonzálvez ML, Lainez N, Castellano D, García-Carbonero I, Esteban E, Sáez MI, Villatoro R, Suárez C, Carrato A, Munárriz-Ferrándiz J, Basterrechea L, García-Alonso M, González-Larriba JL, Perez-Valderrama B, Cruz-Jurado J, González Del Alba A, Moreno F, Reynés G, Rodríguez-Remírez M, Boni V, Mahillo-Fernández I, Martin Y, Viqueira A, García-Foncillas J. Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib. Sci Rep. 2017 Jan 24;7:41371
  32. Gonzalez-Billalabeitia E, Castellano D, Sobrevilla N, Guma J, Hervas D, Luengo MI, Aparicio J, Sanchez-Muñoz A, Mellado B, Saenz A, Valverde C, Fernandez A, Margeli M, Duran I, Fernandez S, Sastre J, Ros S, Maroto P, Manneh R, Cerezuela P, Carmona-Bayonas A, Ayala de la Peña F, Aguilar JL, Rivera S, García del Muro X, Germà-Lluch JR; Spanish Germ Cell Cancer Group/Grupo Germinal (SGCCG). Prognostic Significance of Venous Thromboembolic Events in Disseminated Germ Cell Cancer Patients.J Natl Cancer Inst. 2017 Jan 25;109(4)

PROJECTS

  • Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC).
    Reference: RISC
    Principal Investigator: Rafael Morales
  • Estudio observacional prospectivo de modelos de tratamiento y resultados del tratamiento en el mundo real en pacientes con carcinoma de células renales avanzado o metastásico que reciben pazopanib.
    Reference: VEG115231 PRINCIPAL
    Principal Investigator: Cristina Suárez
  • Estudio del Efecto a Largo Plazo de La Quimioterapia en Pacientes con Tumores de Células Germinales de Testículo. Incidencia del Síndrome Metabólico. GG-11-02.
    Reference: Estudio Síndrome metabólico (Grupo Germinal)
    Principal Investigator: Claudia Valverde
  • Papel de Insulin Growth Factor Receptor en la resistencia intrínseca y adquirida a Imatinib en pacientes con GIST.
    Reference: GEIS 26
    Principal Investigator: Claudia Valverde
  • Sequence in men with metastasic castration-resistant prostate cancer: a European, retrospective, observational study.
    Reference: CATS
    Principal Investigator: Rafael Morales
  • Estudio de cDNA en cáncer de próstata resistente a la castración. (SEROTECA).
    Reference: Seroteca
    Principal Investigator: Joan Carles
  • Marcadores circulantes en pacientes con carcinoma renal avanzado o metastásico en primera línea de tratamiento.
    Reference: SOG-ITQ-2013-01 (EPA)
    Principal Investigator: Cristina Suárez
  • Estudio prospectivo multicéntrico de factores pronósticos en cáncer de próstata resistente a la castración tratados con docetaxel o Cabazitaxel.
    Reference: ProsAbi
    Principal Investigator: Rafael Morales
  • Estudio prospectivo multicéntrico de factores pronósticos en cáncer de próstata resistente a la castración tratados con docetaxel o Cabazitaxel.
    Reference: Prosrad
    Principal Investigator: Rafael Morales (Coordinador Nacional)
  • Estudio prospectivo multicéntrico de factores pronósticos en cáncer de próstata resistente a la castración tratados con Acetato de Abiraterona.
    Reference: Prostac
    Principal Investigator: Rafael Morales
  • Proyecto Prosenza: Estudio prospectivo multicéntrico de factores pronósticos en pacientes con cáncer de PROStata resistentes a la castración con ENZAlutamida.
    Principal Investigator: Rafael Morales
  • Proyecto Proradium_ Estudio prospectivo de factores pronóticos en pacientes con cáncer de próstata resistentes a la castración tratados con Radium-223
    Principal Investigator: Rafael Morales
  • CTC-SOGUG: Determinación de CTCs en el seguimiento de enfermos tratados con Radium 223.
    Principal Investigator: Joan Carles
  • Seguimiento clínico postorquiectomía en pacientes sin invasión de la rete testis y quimioterapia adyuvante con 2 ciclos de carboplatino en aquellos con invasión de la rete testis.
    Principal Investigator: Claudia Valverde
  • Estudio de factores de susceptibilidad genética en Cáncer de Testículo (Colaboración CNIO multicéntrico nacional).
    Principal Investigator: Claudia Valverde
  • Estudio de mecanismos de resistencia a antiangiogénicos (ICO).
    Principal Investigator: Cristina Suárez
  • Análisis comparativo de patrones micro RNAs de riñones embrionarios y tumores renales.
    Principal Investigator: Cristina Suárez
  • Modelo de Avatar PDX para predicción de la sensibilidad a fármacos en tumores renales.
    Principal Investigator: Cristina Suárez
  • SPAZO 2: Pazopanib en la vida real.
    Principal Investigator: Cristina Suárez
  • Perfil genético mutacional en pacientes con cáncer renal metastásico tratados con inhibidores de mTOR.
    Principal Investigator: Cristina Suárez
  • Senescencia en Sarcomas y GIST.
    Principal Investigator: Claudia Valverde
  • Colaboración en distintas bases de datos: Germinales, Sarcomas de partes blandas, Osteosarcomas y GIST (GEIS), Carcinoma Suprarrenal (GETHI).
    Principal Investigator: Claudia Valverde
  • Estudio observacional, retrospectivo y multicéntrico que evalúa los tratamientos de segunda línea en pacientes con sarcoma de tejidos blandos, localmente avanzados o metastáticos, tratados con Pazopanib.
    Reference: GEIS 41
    Principal Investigator: Claudia Valverde
  • Papel de HER-3 en TMVNP esporádico y asociado a NF-1.
    Principal Investigator: Claudia Valverde
  • Estudio observacional, retrospectivo y multicéntrico que evalúa los tratamientos de segunda línea en pacientes con sarcoma de tejidos blandos, localmente avanzados o metastásicos, que progresan a antraciclinas y/o ifosfamida.
    Reference: GEIS38
    Principal Investigator: Claudia Valverde
  • Identificación de biocamarcadores pronósticos y predictivos de respuesta a quimioterapia en el osteosarcoma de alto grado. Estudio nacional sobre un registro retrospectivo.
    Reference: GEIS44
    Principal Investigator: Claudia Valverde
  • Estudio Observacional retrospectivo de pacientes con tumores del estroma gastrointestinal (GIST), metastásico o localmente avanzado, tratados con sunitinib. Análisis exploratorio de factores pronósticos y predictivos en largos respondedores.
    Reference: GEIS43
    Principal Investigator: Claudia Valverde
  • Prognostic relevance of miRNA let-7e in localized intestinal GIST. A Spanish Group for Research on Sarcoma (GEIS) study.
    Principal Investigator: Claudia Valverde
  • Estudio observacional de largos respondedores GIST.
    Reference: GEIS45
    Principal Investigator: Claudia Valverde
  • Caracterización molecular del CP en función de la expresión TMPRSS2-ERG: Implicaciones terapéuticas.
    Principal Investigator: Cristina Suárez
  • Análisis retrospectivo de la influencia de: AAS, Antilipolipemiantes e hipoglicemiantes en la evolución del CPRC.
    Principal Investigator: Joan Carles
  • Academic Collaboration in a Clinical Trial: Calypso MEDI4736 Combinations in Metastasic Renal Cell Carcinoma, Queen Mary University of London.
    01/06/2016 - 31/12/2017

Gynecological Malignancies Group

Imagen

Principal Investigator
Ana Oaknin

Medical Oncologist and Clinical Fellows
Lorena Fariñas
Jose Loureiro
Maria Roca
Víctor Rodríguez

Clinical Nurse Specialist
Cristina Casal

SUMMARY

Our group focuses on clinical research in gynecological malignancies and the development of novel therapies against these tumors. Notably, over the past few years, our clinical studies have led to the approval of a new standard of care in both resistant relapsed ovarian cancer (e.g. the AURELIA Trial), and metastatic cervical cancer (e.g. GOG240 trial). Our research has led to important advancements throughout 2017. Of particular reference has been our involvement in the development of Rucaparib.

Rucaparib belongs to the family of novel agents known as PARP inhibitors and has recently been approved by the FDA for patients with ovarian cancer with BRCA mutations, and we are now focused on obtaining this same approval in Europe. Importantly, most of our clinical research is carried out in close collaboration and connectivity with other international research groups of excellence.

To further develop PARP inhibitors, we aim to identify resistance mechanisms to these agents. This important research is being performed using patient-derived xenograft models (PDX). We obtain biopsies from patients for whom the agents are no longer active and through ex vivo implantation in mice, we will analyze their molecular characteristics and test new drugs that may overcome primary resistance.

We are also actively working on the development of immunotherapeutic agents for patients with gynecologic tumors, and are involved in Phase I studies to test the efficacy and toxicity profile in a particular subgroup of gynecological tumors, namely, endometrial cancer. Therapeutic options for patients diagnosed with relapsed endometrial cancer are currently limited. The emerging suite of novel immunotherapeutics is opening up new treatment opportunities.

As part of an international collaboration, we will also be pioneering cellular therapy for patients with metastatic and/or recurrent cervical cancer. Adoptive cell transfer of tumor infiltrating lymphocytes (TILs) represents a potentially effective treatment for patients with cervical cancer. This method involves the recovery and ex vivo expansion of autologous antitumor lymphocytes that have infiltrated a patient's tumor. TILs isolated from human cervical tumors and expanded ex vivo have shown anti-tumor activity. Preliminary data from this therapeutic approach show great promise and VHIO will play an active role in developing this adoptive therapy for our young patients with cervical cancer.

We are active members of some of the most relevant societies in gynecological oncology including the Gynecologic Cancer Inter Group (GCIG), for which we are appointed as the Spanish Representative on the Cervical Cancer Committee, the Gynecologic Oncology Group (GOG), as Spanish Clinical Lead, as well as the European Network of Gynecological Oncology Trial Groups (ENGOT). Our group's Principal Investigator, Ana Oaknin, serves on the Executive Board as Vice President for the Grupo Español de Investigación en Cáncer de Ovario - GEICO (Spanish Gynecological Group). These roles enable us to initiate the development of new drugs and novel treatment approaches from the very outset, providing our patients with greater opportunity to potentially benefit from these advances in cancer therapeutics.

In addition, Víctor Rodriguez-Freixinos as a senior staff Medical Oncologist of the Gynecologic Cancer and Drug Development Program at the Vall d'Hebron University Hospital, (Vall d'Hebron Barcelona Hospital Campus), has been appointed as member of GEICO's Scientific Committee and its representative in the ENGOT Rare Tumor Group initiative.

It is thanks to our expanding clinical research of excellence that we are potentiating more effective therapies for the treatment and management of gynecological tumors. As a renowned leader within the field, we are also the Reference Site for the majority of regional hospitals and sites at national level. This has consequently led to a steady increase in the number of patients treated with new therapies enrolled in our clinical trials and, most importantly, provided new hope for these patients.

In parallel, we are key members of multidisciplinary committees and teams in gynecological tumors at the Vall d'Hebron University Hospital (HUVH). Our involvement, in partnership with other professionals and specialties (including surgeons, radiotherapists, radiologists, and pathologists), leads to new treatment protocols and clinical guidelines to further improve clinical practice at our hospital.

Moreover, over the past year, we have established a regional collaborative group – our Gynecologic Task Force. This team is composed of a variety of disciplines involved in gynecological tumors. We currently count on the expertise of a pathologist, gynecologist, genetic counselors and a medical oncologist from the Hospitals of the Catalan Institute of Oncology (ICO), and VHIO. The aim of this group is to exchange experiences, share expertise and collectively develop clinical research projects.

We are continuously invited to participate at international conferences of excellence through the delivery of presentations, invited lectures, and the sharing of our latest findings with colleagues and peers at the most prestigious oncology meetings across the globe.

Our group's Principal Investigator, Ana Oaknin, is currently Faculty Member of the Education Program for the Gynecologic Tumors Track for the forthcoming 2018 Congress of the European Society for Medical Oncology (ESMO), 19 – 23 October, Munich, Germany, and has been appointed as Chair, Gynecological Cancers, for ESMO's 2019 Congress, 27 September – 01 October, Barcelona, Spain.

STRATEGIC GOALS

  • Determine the best treatment approaches in advanced gynecologic malignancies through well designed international clinical trials.
  • Contribute to early drug development in gynecologic malignancies.
  • Build a translational research program to advance precision medicine.

HIGHLIGHTS

  • As a result of our clinical research of excellence, we continue to lead pivotal studies in gynecological malignancies which could potentially change the standard of care.
  • As lead investigator for GOG in Spain, our group is heading a Phase III clinical trial in advanced cervical cancer with a novel vaccine to prevent and/or delay disease recurrence.
  • Our involvement in several international cooperative groups of excellence further enables us to participate in outstanding clinical research programs.
  • Ana Oaknin's Vice Presidency of the GEICO group. This role has allowed our group to help lead clinical research in gynecological malignancies throughout Spain.
  • The involvement of our principal investigator, Ana Oaknin, in ESMO's Educational Program of its next two annual Congresses further reinforces our position within Europe as a reference site.

PI PAPER PICK (full list for 2017 below)

Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961

Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663.

Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87.

Oaknin A, Guarch R, Barretina P, Hardisson D, González-Martín A, Matías-Guiu X, Pérez-Fidalgo A, Vieites B, Romero I, Palacios J. Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol. 2017 Aug 16.

HORIZONS 2018

  • Our group is working on identifying the mechanisms of resistance to PARP inhibitors in ovarian cancer patients. This work will be carried out through a close collaboration between clinicians and preclinical researchers at VHIO.
  • We will apply cellular therapy to metastatic cervical cancer through the adoptive cell transfer of tumor infiltrating lymphocytes (TIL).
  • We will further develop novel immunotherapeutics for the treatment of endometrial cancer.
  • We will consolidate the Gynecologic Task Force as a leading research group.
  • Continue to act as a referral center for patients who wish to participate and receive treatment in our clinical studies.

PUBLICATIONS

  1. OakninA, Guarch R, Barretina P, Hardisson D, González-Martín A, Matías-Guiu X, Pérez-Fidalgo A, Vieites B, Romero I, Palacios J. Erratum to: Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology.  Clin Transl Oncol. 2017 Sep 20. doi: 10.1007/s12094-017-1746-7. [Epub ahead of print]
  2. Coleman RL, Oza AM, Lorusso D, Aghajanian C, OakninA, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28; 390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
  3. Oza AM, Tinker AV, OakninA, Shapira-Frommer R, McNeish IA, Swisher EM, Ray-Coquard I, Bell-McGuinn K, Coleman RL, O'Malley DM, Leary A, Chen LM, Provencher D, Ma L, Brenton JD, Konecny GE, Castro CM, Giordano H, Maloney L, Goble S, Lin KK, Sun J, Raponi M, Rolfe L, Kristeleit RS. Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 and ARIEL2.Gynecol Oncol. 2017 Nov; 147(2):267-275.doi: 10.1016/j.ygyno.2017.08.022. Epub 2017 Sep 4.
  4. OakninA, Guarch R, Barretina P, Hardisson D, González-Martín A, Matías-Guiu X, Pérez-Fidalgo A, Vieites B, Romero I, Palacios. Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol.2017 Sep 20.doi: 10.1007/s12094-017-1746-7.
  5. Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet Oncol. 2017 Jan; 18(1):75-87. doi: 10.1016/S1470-2045(16)30559-9. Epub 2016 Nov 29.
  6. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, OakninA, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.Lancet Oncol. 2017 Jan; 18(1):75-87. doi: 10.1016/S1470-2045(16)30559-9. Epub 2016 Nov 29.
  7. Pautier P,Vergote I, Joly F, Melichar B, Kutarska E, Hall G, Lisyanskaya A, Reed N, Oaknin A, Ostapenko V, Zvirbule Z, Chetaille E, Geniaux A, Shoaib M, Green JA.A Phase 2,Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer. Int J Gynecol Cancer. 2016 Nov 17

PROJECTS

  • Recurrent SMARCA4 mutations in small cell carcinoma of the ovarian
    Principal Investigator: Ana Oaknin
    Supported by a FERO Grant
  • Function, Diagnostic Value and Pharmacologic Evaluation of R-RAS2: a new oncogenic driver.
    Global Principal Investigator: Xosé Ramon Bustelo
    Principal Investigator at VHIO: Ana Oaknin
    Supported by a FERO Grant

AWARDS AND RECOGNITION

  • Our Principal investigator, Ana Oaknin, has been appointed as Chair of the Gynecologic Tumors Track for the 2019 Congress of the European Society for Medical Oncology (ESMO), 27 September – 01 October, Barcelona, Spain.

High Risk & Cancer Prevention Group

Imagen

Principal Investigator
Judith Balmaña

Staff Scientists
Estela Carrasco
Marta Codina
Cristina Cruz
Adriá López
Neda Stjepanovic

Auxiliary Clinician
Carmen Aguilar

Clinical Nurse Specialist
Neus Gadea

Data Curator
Sara Torres

SUMMARY

We develop novel targeted therapies for patients with breast cancer and a genetic susceptibility. During 2017, patients with local and advanced breast cancer and a BRCA germline mutation participated in several phase II/III trials with a specific DNA binding agent or PARP inhibitor.

The consolidation of our collaboration with VHIO's Experimental Therapeutics Group, led by Violeta Serra, has resulted in a large collection of BRCA-associated patient-derived xenografts (PDX) implanted in athymic mice. We are using these murine models to identify mechanisms of resistance to targeted therapies, identify novel biomarkers and assess new combinatorial treatments at progression. We have focused on identifying a biomarker for PARP inhibitor sensitivity. A functional biomarker of homologous recombination has been tested both preclinically and in human samples, with validation ongoing. Two mechanisms of resistance to PARP inhibitors have been evidenced in our cohort of PDX samples.

In the field of genetic epidemiology, we mainly focus on identifying new genetic susceptibilities to hereditary breast cancer. Analysis of a panel of 98 cancer susceptibility genes in 193 breast and/or ovarian cancer families with no mutation in BRCA1/BRCA2 has been finalized and we have now submitted our findings as a scientific article. We are also committed to performing co-segregation analysis in these families and investigating the cancer spectrum and phenotype of these lesser-known non-BRCA genes.

We have finalized our psychological study of the impact of multigene cancer panel testing in more than 200 centres across Spain.

In hereditary colorectal cancer, we are participating in a clinical study led by the EPICOLON group to gauge cancer risk estimates in Lynch Syndrome mutation carriers.

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Figure: Psychological impact (MICRA scale) of multi-gene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

STRATEGIC GOALS

  • Clinical development of specific therapeutic strategies for tumors associated with hereditary genetic alterations.
  • Testing new combinations of therapies for BRCA-associated PDXs that have progressed to PARP inhibitors.
  • Identification of new genes involved in hereditary breast cancer through the application of next generation sequencing (NGS).
  • The yield of multigene panel testing in hereditary cancer syndromes and its impact on patient care.
  • Psychological impact of hereditary cancer multiplex gene testing in the Spanish population.

HIGHLIGHTS

  • Active participation in international phase II and phase III clinical trials with targeted therapies for BRCA-associated tumors.
  • Identification of a functional biomarker of homologous recombination deficiency and PARPi sensitivity in preclinical models.
  • Analysis of the rate of pathogenic variants in phenotype-driven panels versus core panels in patients with hereditary cancer, the yield of opportunistic testing, and actionability of novel breast and ovarian cancer susceptibility genes.

PI PAPER PICK (full list for 2017 below)

Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4095-4106.

Esteban-Jurado C, Giménez-Zaragoza D, Muñoz J, Franch-Expósito S, Álvarez-Barona M, Ocaña T, Cuatrecasas M, Carballal S, López-Cerón M, Marti-Solano M, Díaz-Gay M, van Wezel T, Castells A, Bujanda L, Balmaña J, Gonzalo V, Llort G, Ruiz-Ponte C, Cubiella J, Balaguer F, Aligué R, Castellví-Bel S. POLE and POLD1 screening in 155 patients with multiple polyps and eardly-onset colorectal cancer. Oncotarget. 2017 April 18:8(16): 26732-26743.

Egoavil C, Juárez M, Guarinos C, Rodríguez-Soler M, Hernández-Illán E, Alenda C, Payá A, Castillejo A, Serradesanferm A, Bujanda L, Fernández-Bañares F, Cubiella J, de-Castro L, Guerra A, Aguirre E, Herreros-de-Tejada A, Bessa X, Herráiz M, Marín-Gabriel JC, Balmaña J, Piñol V, Rodríguez Moranta F, Nicolás-Pérez D, Cuatrecasas M, Balaguer F, Castells A, Soto JL, Zapater P, Jover R. Increased risk of colorectal cancer in patients with multiples serrated polyps and their first-degree relatives. Gastroenterology. 2017 Jul; 153(1):106-112

HORIZONS 2018

  • Continue to participate in phase III clinical trials with targeted therapies in BRCA-associated breast and ovarian cancer. Promote clinical trials with drug-drug combinatorial targeted therapies and chemotherapy in this population.
  • Identify mechanisms of resistance to targeted therapies in BRCA-associated breast cancer and functional biomarkers of sensitivity/resistance.
  • Identify clinical and molecular predictors of bad prognosis in gBRCA-associated early breast cancer.
  • Test novel combinations of targeted therapies in a patient-derived xenograft model from patients with a germline BRCA mutation.
  • Investigate the prevalence, cancer spectrum, phenotype, and clinical utility of non-BRCA breast cancer susceptibility genes.
  • Investigate the association between traits of personality and psychological impact of multiplex cancer panel testing.

PUBLICATIONS

  1. Balmaña J, Digiovanni L, Gaddam P, Walsh MF, Joseph V, Stadler ZK, Nathanson KL, Garber JE, Couch FJ, Offit K, Robson ME, Domchek SM. Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. J Clin Oncol.2016 Dec;34(34):4071-4078.
  2. Balmaña J, Nathanson K, Robson M, Domchek S. Reply to R. Nussbaum et al and J. Dolinsky et al. J Clin Oncol. 2017, Jan 30.
  3. Kristeleit R, Shapiro GI, Burris HA, Oza AM, Lo Russo PM, Patel M, Domcheck SM, Balmaña J,drew Y, Chen LM, Safra T, montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I-II Study of the Oral Poly (ADP-ribose) Polymerase Inhibitor Rucaparib in Patients with Germline BRCA1/2-mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017.
  4. Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, Dennis J, Pirie A, Riggan MJ, Chornokur G, Earp MA, Lyra PC Jr, Lee JM, Coetzee S, Beesley J, McGuffog L, Soucy P, Dicks E, Lee A, Barrowdale D, Lecarpentier J, Leslie G, Aalfs CM, Aben KKH, Adams M, Adlard J, Andrulis IL, Anton-Culver H, Antonenkova N; AOCS study group., Aravantinos G, Arnold N, Arun BK, Arver B, Azzollini J, Balmaña J,Banerjee SN, Barjhoux L, Barkardottir RB, Bean Y, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini MQ, Birrer MJ, Bjorge L, Black A, Blankstein K, Blok MJ, Bodelon C, Bogdanova N, Bojesen A, Bonanni B, Borg Å, Bradbury AR, Brenton JD, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Bruinsma F, Brunet J, Buecher B, Butzow R, Buys SS, Caldes T, Caligo MA, Campbell I, Cannioto R, Carney ME, Cescon T, Chan SB, Chang-Claude J, Chanock S, Chen XQ, Chiew YE, Chiquette J, Chung WK, Claes KBM, Conner T, Cook LS, Cook J, Cramer DW, Cunningham JM, D'Aloisio AA, Daly MB, Damiola F, Damirovna SD, Dansonka-Mieszkowska A, Dao F, Davidson R, DeFazio A, Delnatte C, Doheny KF, Diez O, Ding YC, Doherty JA, Domchek SM, Dorfling CM, Dörk T, Dossus L, Duran M, Dürst M, Dworniczak B, Eccles D, Edwards T, Eeles R, Eilber U, Ejlertsen B, Ekici AB, Ellis S, Elvira M; EMBRACE Study., Eng KH, Engel C, Evans DG, Fasching PA, Ferguson S, Ferrer SF, Flanagan JM, Fogarty ZC, Fortner RT, Fostira F, Foulkes WD, Fountzilas G, Fridley BL, Friebel TM, Friedman E, Frost D, Ganz PA, Garber J, García MJ, Garcia-Barberan V, Gehrig A; GEMO Study Collaborators., Gentry-Maharaj A, Gerdes AM, Giles GG, Glasspool R, Glendon G, Godwin AK, Goldgar DE, Goranova T, Gore M, Greene MH, Gronwald J, Gruber S, Hahnen E, Haiman CA, Håkansson N, Hamann U, Hansen TVO, Harrington PA, Harris HR, Hauke J; HEBON Study., Hein A, Henderson A, Hildebrandt MAT, Hillemanns P, Hodgson S, Høgdall CK, Høgdall E, Hogervorst FBL, Holland H, Hooning MJ, Hosking K, Huang RY, Hulick PJ, Hung J, Hunter DJ, Huntsman DG, Huzarski T, Imyanitov EN, Isaacs C, Iversen ES, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, Jernetz M, Jensen A, Jensen UB, John EM, Johnatty S, Jones ME, Kannisto P, Karlan BY, Karnezis A, Kast K; KConFab Investigators., Kennedy CJ, Khusnutdinova E, Kiemeney LA, Kiiski JI, Kim SW, Kjaer SK, Köbel M, Kopperud RK, Kruse TA, Kupryjanczyk J, Kwong A, Laitman Y, Lambrechts D, Larrañaga N, Larson MC, Lazaro C, Le ND, Le Marchand L, Lee JW, Lele SB, Leminen A, Leroux D, Lester J, Lesueur F, Levine DA, Liang D, Liebrich C, Lilyquist J, Lipworth L, Lissowska J, Lu KH, Lubinński J, Luccarini C, Lundvall L, Mai PL, Mendoza-Fandiño G, Manoukian S, Massuger LFAG, May T, Mazoyer S, McAlpine JN, McGuire V, McLaughlin JR, McNeish I, Meijers-Heijboer H, Meindl A, Menon U, Mensenkamp AR, Merritt MA, Milne RL, Mitchell G, Modugno F, Moes-Sosnowska J, Moffitt M, Montagna M, Moysich KB, Mulligan AM, Musinsky J, Nathanson KL, Nedergaard L, Ness RB, Neuhausen SL, Nevanlinna H, Niederacher D, Nussbaum RL, Odunsi K, Olah E, Olopade OI, Olsson H, Olswold C, O'Malley DM, Ong KR, Onland-Moret NC; OPAL study group., Orr N, Orsulic S, Osorio A, Palli D, Papi L, Park-Simon TW, Paul J, Pearce CL, Pedersen IS, Peeters PHM, Peissel B, Peixoto A, Pejovic T, Pelttari LM, Permuth JB, Peterlongo P, Pezzani L, Pfeiler G, Phillips KA, Piedmonte M, Pike MC, Piskorz AM, Poblete SR, Pocza T, Poole EM, Poppe B, Porteous ME, Prieur F, Prokofyeva D, Pugh E, Pujana MA, Pujol P, Radice P, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rhiem K, Rice P, Richardson A, Robson M, Rodriguez GC, Rodríguez-Antona C, Romm J, Rookus MA, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Salvesen HB, Sandler DP, Schoemaker MJ, Senter L, Setiawan VW, Severi G, Sharma P, Shelford T, Siddiqui N, Side LE, Sieh W, Singer CF, Sobol H, Song H, Southey MC, Spurdle AB, Stadler Z, Steinemann D, Stoppa-Lyonnet D, Sucheston-Campbell LE, Sukiennicki G, Sutphen R, Sutter C, Swerdlow AJ, Szabo CI, Szafron L, Tan YY, Taylor JA, Tea MK, Teixeira MR, Teo SH, Terry KL, Thompson PJ, Thomsen LCV, Thull DL, Tihomirova L, Tinker AV, Tischkowitz M, Tognazzo S, Toland AE, Tone A, Trabert B, Travis RC, Trichopoulou A, Tung N, Tworoger SS, van Altena AM, Van Den Berg D, van der Hout AH, van der Luijt RB, Van Heetvelde M, Van Nieuwenhuysen E, van Rensburg EJ, Vanderstichele A, Varon-Mateeva R, Vega A, Edwards DV, Vergote I, Vierkant RA, Vijai J, Vratimos A, Walker L, Walsh C, Wand D, Wang-Gohrke S, Wappenschmidt B, Webb PM, Weinberg CR, Weitzel JN, Wentzensen N, Whittemore AS, Wijnen JT, Wilkens LR, Wolk A, Woo M, Wu X, Wu AH, Yang H, Yannoukakos D, Ziogas A, Zorn KK, Narod SA, Easton DF, Amos CI, Schildkraut JM, Ramus SJ, Ottini L, Goodman MT, Park SK, Kelemen LE, Risch HA, Thomassen M, Offit K, Simard J, Schmutzler RK, Hazelett D, Monteiro AN, Couch FJ, Berchuck A, Chenevix-Trench G, Goode EL, Sellers TA, Gayther SA, Antoniou AC, Pharoah PDP.Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017 May; 49(5): 680-691.
  5. Egoavil C, Juarez M, Guarinos C, Rodríguez-Soler M, Hernández-Illán E, Alenda C, Payá A, Castillejo A, Serradesanferm A, Bujanda L, Fernández-Bañares F, Cubiella J, de-Castro L, Guerra A, Aguirre E, Herreros-de-Tejada A, Bessa X, Herráiz M, Marín-Gabriel JC, Balmaña J, Piñol V, Cuatrecasas M, Balaguer F, Castells A, Soto JL, Zapater P, Jover R. Increased Risk of Colorectal Cancer in Patients With Multiple Serrated Polyps and Their First-degree Relatives. Gastroenterology, 2017 Apr. 8.
  6. Esteban-Jurado C, Giménez-Zaragoza D, Muñoz J, Franch-Expósito S, Álvarez-Barona M, Ocaña T, Cuatrecasas M, Carballal S, López-Cerón M, Marti-Solano M, Díaz-Gay M, van Wezel T, Castells A, Bujanda L, Balmaña J, Gonzalo V, Llort G, Ruiz-Ponte C, Cubiella J, Balaguer F, Aligué R, Castellví-Bel S. POLE and POLD1 screening in 155 patients with multiple polyps and early-onset colorectal cancer. Oncotarget, 2017 Apr 18;8(16): 26732-26743.
  7. Lecarpentier J, Silvestri V, Kuchenbaecker KB, Barrowdale D, Dennis J, McGuffog L, Soucy P, Leslie G, Rizzolo P, Navazio AS, Valentini V, Zelli V, Lee A, Amin Al Olama A, Tyrer JP, Southey M, John EM, Conner TA, Goldgar DE, Buys SS, Janavicius R, Steele L, Ding YC, Neuhausen SL, Hansen TVO, Osorio A, Weitzel JN, Toss A, Medici V, Cortesi L, Zanna I, Palli D, Radice P, Manoukian S, Peissel B, Azzollini J, Viel A, Cini G, Damante G, Tommasi S, Peterlongo P, Fostira F, Hamann U, Evans DG, Henderson A, Brewer C, Eccles D, Cook J, Ong KR, Walker L, Side LE, Porteous ME, Davidson R, Hodgson S, Frost D, Adlard J, Izatt L, Eeles R, Ellis S, Tischkowitz M; EMBRACE., Godwin AK, Meindl A, Gehrig A, Dworniczak B, Sutter C, Engel C, Niederacher D, Steinemann D, Hahnen E, Hauke J, Rhiem K, Kast K, Arnold N, Ditsch N, Wang-Gohrke S, Wappenschmidt B, Wand D, Lasset C, Stoppa-Lyonnet D, Belotti M, Damiola F, Barjhoux L, Mazoyer S; GEMO Study Collaborators., Van Heetvelde M, Poppe B, De Leeneer K, Claes KBM, de la Hoya M, Garcia-Barberan V, Caldes T, Perez Segura P, Kiiski JI, Aittomäki K, Khan S, Nevanlinna H, van Asperen CJ; HEBON., Vaszko T, Kasler M, Olah E, Balmaña J,Gutiérrez-Enríquez S, Diez O, Teulé A, Izquierdo A, Darder E, Brunet J, Del Valle J, Feliubadalo L, Pujana MA, Lazaro C, Arason A, Agnarsson BA, Johannsson OT, Barkardottir RB, Alducci E, Tognazzo S, Montagna M, Teixeira MR, Pinto P, Spurdle AB, Holland H; KConFab Investigators., Lee JW, Lee MH, Lee J, Kim SW, Kang E, Kim Z, Sharma P, Rebbeck TR, Vijai J, Robson M, Lincoln A, Musinsky J, Gaddam P, Tan YY, Berger A, Singer CF, Loud JT, Greene MH, Mulligan AM, Glendon G, Andrulis IL, Toland AE, Senter L, Bojesen A, Nielsen HR, Skytte AB, Sunde L, Jensen UB, Pedersen IS, Krogh L, Kruse TA, Caligo MA, Yoon SY, Teo SH, von Wachenfeldt A, Huo D, Nielsen SM, Olopade OI, Nathanson KL, Domchek SM, Lorenchick C, Jankowitz RC, Campbell I, James P, Mitchell G, Orr N, Park SK, Thomassen M, Offit K, Couch FJ, Simard J, Easton DF, Chenevix-Trench G, Schmutzler RK, Antoniou AC, Ottini L. Prediction of Breast and Cancer Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. J Clin Oncol. 2017, Apr 27.

PROJECTS

  • Identification of Molecular Prognostic Predictors in gBRCA-Associated Breast Cancer and Analysis of New Therapeutic Strategies
    AECC Grant
    Principal Investigator: Cristina Cruz
  • Identification of new phenotypes associated to Hereditary Cancer through the use of Gene Panels; Impact in patients' medical and psychological care
    Reference: FIS- PI1601363
    Principal investigator: Judith Balmaña

Oncogenetics Group

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Principal Investigator
Orland Díez

Senior Scientist
Sara Gutiérrez

Post-Doctoral Fellow
Sandra Bonache

Clinical Nurse Specialist
Bibiana Piqué

Graduate Students
Laura Durán
Alejandro Moles
Gemma Montalban

SUMMARY

We focus on two main lines of research: 1) the genetic predisposition to hereditary cancer, and 2) genetic predisposition to radiotherapy-induced toxicity.

Inherited predisposition to breast and ovarian cancer is caused by an expanding list of genes such as BRCA1, BRCA2, PALB2, RAD51C, RAD51D and TP53. We search for other alleles and new genes that may predispose to these types of cancer using massive sequencing to analyze panel genes and whole exomes.

Due to high allelic heterogeneity many results from genetic testing are variants with unknown clinical significance (VUS). The analysis of these variants and other alterations in untranslated regions in genes of clinical significance constitutes another major focus of our research.

We carry out splicing studies, in silico analyses, and collaborate with other partners in international consortia including the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), to develop multifactorial studies aimed at ascertaining the effect of VUS. We are also working to establish a biological model derived from the carriers themselves through which to evaluate the in vitro functional effect of VUS and determine their potential pathogenicity. In addition, we are testing the most suitable bioinformatics prediction algorithms to select the variants that cause aberrant gene splicing in familial cancer genes.

Similarly, in collaboration with the Vall d'Hebron Research Institute's (VHIR) Translational Bioinformatics Group headed by X. de la Cruz, we participate in the development of a novel in silico tool to evaluate the effect of BRCA1/2 genetic variants identified in patients with cancer predisposition.

As a partner of the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), we collaborate in wide case-control studies to identify low-penetrance alleles and genes that modify penetrance of BRCA1/2 pathogenic variants.

We also collaborate with VHIO's High Risk & Cancer Prevention and Experimental Therapeutics Groups to analyze the role of expression changes in new or natural BRCA1 mRNA isoforms as a mechanism of resistance to PARP inhibitors using patient-derived tumor xenografts (PDXs).

Around half of all cancer patients receive radiotherapy and among 3-5% of them suffer from severe long-term side-effects. Current evidence suggests the heritability of radiosensitivity. We are participating in the European Commission FP7-funded REQUITE international study, Validating Predictive Models and Biomarkers of Radiotherapy Toxicity to Reduce Side-Effects and Improve Quality of Life in Cancer Survivors, to identify potential genetic and cellular markers for radiotherapy toxicity. As member of the International Consortium of Radiogenomics we perform meta-analysis to confirm the association between different SNPs and toxicity post-radiotherapy.

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Figure: Identification of allelic loss in BRCA2 gene in tumoral tissue.

STRATEGIC GOALS

  • As member of the Catalan Cancer Network's Hereditary Cancer Program, decipher the spectrum, frequency and clinical actionability of pathogenic variants in cancer predisposing genes in our population.
  • Identify new alleles for the genetic predisposition to hereditary cancer.
  • Perform expression and functional analysis of genetic variants with unknown clinical significance in familiar cancer predisposition.
  • Study genetic variants in regulatory regions of breast/ovarian cancer susceptibility genes that may confer an increased risk.
  • Discover common low-penetrance alleles for breast/ovarian cancer risk.
  • Analyze BRCA1/2 tumoral expression in response to therapy.
  • Identify cellular and molecular biomarkers for the prediction of late toxicity after radiotherapy.
  • Assess the role of microRNAs and long non coding RNAs in the susceptibility to radiotherapy-induced clinical toxicity.

HIGHLIGHTS

  • Our group has classified genetic variants of unknown clinical significance by expression and functional analyses in the field of hereditary cancer predisposition.
  • The massive sequencing of large gene panels and exomes to identify new susceptibility alleles to familial breast/ovarian cancer, and confirmation of candidate genes in collaboration with the COMPLEXO Consortium.
  • We have tested the most suitable bioinformatics prediction algorithms to identify splicing variants in familial cancer genes.
  • In partnership with the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), we have described new alleles of breast/ovarian cancer susceptibility and modifiers of risk conferred by BRCA1/2 pathogenic variants.
  • We have enrolled breast and lung cancer patients in the European Commission FP7-funded project REQUITE to validate predictive models of toxicity from radiotherapy.
  • Our group co-organized and hosted the REQUITE European Project's 5th annual meeting and the 9th Radiogenomics Consortium Meeting, 20-22 June, CELLEX Building, VHIO, Barcelona, with Sara Gutiérrez-Enríquez, Senior Scientist, as Co-Chair.

PI PAPER PICK (full list for 2017 below)

Phelan CM, Kuchenbaecker KB, Tyrer JP, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017 May;49(5):680-691.

Lecarpentier J, Silvestri V, Kuchenbaecker KB, et al. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. J Clin Oncol. 2017 Jul 10;35(20):2240-2250.

Milne RL, Kuchenbaecker KB, Michailidou K et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet. 2017 Dec;49(12):1767-1778.

Hamdi Y, Soucy P, Kuchenbaeker KB, et al. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. Breast Cancer Res Treat. 2017 Jan;161(1):117-134.

HORIZONS 2018

  • To establish the spectrum, frequency and clinical actionability of pathogenic variants in cancer predisposing genes in our population.
  • The bioinformatic analysis of exome sequencing of families with breast cancer to detect putative cancer predisposition genes.
  • Identification and functional characterization of genetic variants located deep intronic or in untranslated regions of BRCA1, BRCA2and other genes.
  • Assess the potential splicing effect of variants with unknown significance (VUS) in clinically actionable genes related to familial breast/ovarian cancer.
  • Establish a functional assay model to evaluate the impact of VUS on cancer risk.
  • Identification of new low penetrance breast and ovarian cancer susceptibility genes and risk modifier genes for BRCA1 and
  • Identification of BRCAmRNA isoforms as a potential novel mechanism of resistance against PARP
  • Participation in the European Commission FP7-funded REQUITE project:Validating predictive models of radiotherapy toxicity to improve quality-of-life and reduce side-effects in cancer survivors.
  • Reveal susceptibility genetic variants in microRNAs and long non-coding RNAs related to radiotherapy-induced clinical toxicity.

PUBLICATIONS

  1. Phelan CM, Kuchenbaecker KB, Tyrer JP, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017 May;49(5):680-691.
  2. Lecarpentier J, Silvestri V, Kuchenbaecker KB, et al. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. J Clin Oncol. 2017 Jul 10;35(20):2240-2250.
  3. Milne RL, Kuchenbaecker KB, Michailidou K et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet. 2017 Dec;49(12):1767-1778.
  4. Hamdi Y, Soucy P, Kuchenbaeker KB, et al. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. Breast Cancer Res Treat. 2017 Jan;161(1):117-134.

PROJECTS

  • Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality-of-life in cancer survivors - REQUITE  (Nº: 601826).
    European Commission FP7
    Local Principal Investigator: Sara Gutiérrez
    2013-2018
  • Análisis del efecto patogénico de variantes genéticas en zonas reguladoras (promotor, 5'UTR y 3'UTR) e intrónicas de BRCA1,BRCA2 y otros genes de susceptibilidad al cáncer de mama y ovario.
    Instituto de Salud Carlos III
    Principal Investigator: Orland Díez
    2016-2018
  • Descubrimiento de nuevos genes y variantes genéticas en cáncer hereditario: estudios funcionales, de regulación del splicing y frecuencia poblacional de las variantes para su aplicación en la clínica.
    Instituto de Salud Carlos III
    Principal Investigator: Sara Gutiérrez-Enríquez
    2017-2019

AWARDS AND RECOGNITION

  • Clinical Research Postdoctoral Fellowship
    Recipient: Sandra Bonache
    Agency: Fundación AECC Investigación contra el Cáncer Duration: 2017-2019
  • Miguel Servet II Contract
    Recipient: Sara Gutiérrez-Enríquez
    Agency: Ministerio de Economía Industria y Competitividad, Instituto Salud Carlos III
    Duration:2017-2020

Oncology Data Science (ODysSey) Group

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Principal Investigator
Rodrigo Dienstmann

Biostatistician
Guillermo Villacampa

Data Curators
Raquel Comas
Fiorella Ruiz
Sara Torres
Cristina Viaplana

Molecular Prescreening Program
Susana Aguilar

SUMMARY

VHIO's ODysSey Group facilitates translational research in precision oncology by integrating latest advances in cancer molecular profiling from patients treated at the Vall d'Hebron University Hospital (HUVH) with their clinical outcome under standard and experimental therapies.

To do so, we design and maintain comprehensive clinical-molecular databases and provide statistical support to investigators interested in correlative analyses for hypothesis-generation and biomarker validation. We also provide standardized reports of next-generation sequencing tests and educate clinicians on the interpretation of these data, thereby offering patients the most appropriate targeted agent and immunotherapy in clinical trials.

Furthermore, we participate in international genomics data sharing projects and foster collaborative research in computational oncology. Our group is dedicated to connecting cancer researchers working on predictive/prognostic modelling, the identification of cancer drivers, intra-tumor heterogeneity, microenvironment signatures and druggability in solid tumors.

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Figure: VHIO's Oncology Data Science (ODysSey) Group's strategic alliances and key collaborations.

STRATEGIC GOALS

    Facilitate clinical-molecular correlative studies at VHIO:
  • Provide guidance to medical oncologists and cancer biologists during the development, validation and interpretation of omics-based tests that have direct clinical application.
  • Development and maintenance of clinical-molecular databases as a resource for medical oncologists, molecular pathologists and translational investigators at VHIO.
  • Promote evidence-based medicine:
  • Maintenance of the publicly available cancer bioMarkers database (part of the Cancer Genome Interpreter webtool - https://www.cancergenomeinterpreter.org/home), a structured database that integrates existing knowledge on tumor types, genes, variants, response/resistance patterns to approved and experimental agents, PubMed identifiers and levels-of-evidence for targetability.
  • Continued medical education with standardized reports of genomic alterations and weekly molecular tumor boards. We facilitate data exchange among a wide range of experts for the review of patient medical histories and cancer molecular profiles in order to more precisely guide treatment decisions.

HIGHLIGHTS

  • We have provided support to VHIO's preclinical and clinical investigators working on biomarker research and its implications for patient management. This has resulted in several impactful publications in the field, as well as presentations at leading oncology congresses.
  • Throughout 2017 we have explored and developed tools that help translate the strong signals of biological dependencies of colorectal cancer subtypes into druggability in clinical practice. We have also studied the impact of driver gene clonality/subclonality patterns and microenvironment features on prognosis and response to matched targeted and immunotherapies in colorectal cancer.
  • Participation in the MedBioinformatics European Consortium: our group has been extensively involved in the development of integrative bioinformatics tools to analyze the huge amount of data and knowledge generated in healthcare and biomedical research in order to advance translational research and precision medicine. Our Cancer Biomarkers database is publicly available and has become a reference for clinical investigators across the globe.

PI PAPER PICK (full list for 2017 below)

Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017;7(2):79-92.

Dienstmann R, Mason MJ, Sinicrope FA, Phipps AI, Tejpar S, Nesbakken A, Danielsen SA, Sveen A, Buchanan DD, Clendenning M, Rosty C, Bot B, Alberts SR, Milburn Jessup J, Lothe RA, Delorenzi M, Newcomb PA, Sargent D, Guinney J. Prediction of overall survival in stage II and III colon cancer beyond the American Joint Commission on Cancer TNM system: a retrospective, pooled biomarker study. Ann Oncol. 2017;28(5):1023-1031.

Dienstmann R, Elez E, Argiles G, Matos I, Sanz-Garcia E, Ortiz C, Macarulla T, Capdevila J, Alsina M, Sauri T, Verdaguer H, Vilaro M, Ruiz-Pace F, Viaplana C, Garcia A, Landolfi S, Palmer HG, Nuciforo P, Rodon J, Vivancos A, Tabernero J. Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights. Mol Oncol. 2017;11(9):1263-1272.

Dienstmann R, Tabernero J. Cancer: A precision approach to tumor treatment. Nature. 2017 Aug 3;548(7665):40-41.

HORIZONS 2018

    Collaborative research on Big Data and Real-World Data:
  • Encourage interactions among computational oncology scientists and preclinical-clinical researchers to promote the identification of cancer drivers, immunophenotypes and study their targetability in solid tumors.
  • Generate large databases for the study of complex correlations between tumour genomics, drug sensitivities and patient outcomes.
  • Active participation in international data-sharing projects (Cancer Core Europe, AACR’s GENIE):
  • Overcome ethical, legal and logistical barriers to aggregate and share cancer genomic data and linked clinical annotation of patients treated at the Vall d’Hebron University Hospital (HUVH). We firmly believe that the statistical power required to improve clinical decision-making, particularly in the case of both rare cancers and genomic variants, requires international collaboration among leading cancer research centers.

PUBLICATIONS

  1. CIViC: A knowledgebase for expert-crowdsourcing the clinical interpretation of variants in cancer. Griffith M, Spies NC, Krysiak K, Coffman AC, McMichael JF, Ainscough BJ, Rieke DJ, Danos AM, Kujan L, Ramirez CA, Wagner AH, Skidmore ZL, Liu CJ, Jones M, Bilski RL, Lesurf R, Barnell EK, Shah NM, Bonakdar M, Trani L, Matlock M, Ramu A, Campbell KM, Spies GC, Graubert AP, Karthik G, Eldred JM, Larson DE, Walker JR, Chu S, Bryan JN, Good BN, Wu C, Su AI, Dienstmann R, Jones SJM, Bose R, Spencer DH, Wartman LD, Wilson RK, Mardis ER, Griffith OL. Nat Genetics 2017;49(2):170-174.
  2. Consensus Molecular Subtyping and the Evolution of Precision Medicine in Colorectal Cancer. Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Nat Rev Cancer 2017;7(2):79-92.
  3. Prediction of overall survival in stage II and III colon cancer beyond the American Joint Commission on Cancer TNM system: a retrospective, pooled biomarker study. DienstmannR, Mason MJ, Sinicrope FA, Phipps AI, Tejpar S, Nesbakken A, Danielsen SA, Sveen A, Buchanan DD, Clendenning M, Rosty C, Bot B, Alberts SR, Milburn Jessup J, Lothe RA, Delorenzi M, Newcomb PA, Sargent D, Guinney J.Ann Oncol2017;28(5):1023-1031.
  4. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Grasselli J, Elez E, Caratù G, Matito J, Santos C, Macarulla T, Vidal J, Garcia M, Viéitez JM, Paéz D, Falcó E, Lopez Lopez C, Aranda E, Jones F, Sikri V, Nuciforo P, Fasani R, Tabernero J, Montagut C, Azuara D, Dienstmann R, Salazar R, Vivancos A. Ann Oncol 2017 Jun 1;28(6):1294-1301.
  5. Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology. Garralda E, Dienstmann R, Tabernero J. Am Soc Clin Oncol Educ Book 2017;37:210-215.
  6. Personalizing Adjuvant Therapy for Stage II/III Colorectal Cancer. McCleary NJ, Benson AB 3rd, Dienstmann R. Am Soc Clin Oncol Educ Book 2017;37:232-245.
  7. Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights. Dienstmann R, Elez E, Argiles G, Matos I, Sanz-Garcia E, Ortiz C, Macarulla T, Capdevila J, Alsina M, Sauri T, Verdaguer H, Vilaro M, Ruiz-Pace F, Viaplana C, Garcia A, Landolfi S, Palmer HG, Nuciforo P, Rodon J, Vivancos A, Tabernero J.Mol Oncol 2017;11(9):1263-1272.
  8. Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells. Roumeliotis TI, Williams SP, Gonçalves E, Alsinet C, Del Castillo Velasco-Herrera M, Aben N, Ghavidel FZ, Michaut M, Schubert M, Price S, Wright JC, Yu L, Yang M, Dienstmann R, Guinney J, Beltrao P, Brazma A, Pardo M, Stegle O, Adams DJ, Wessels L, Saez-Rodriguez J, McDermott U, Choudhary JS. Cell Rep 2017;20(9):2201-2214.
  9. Cancer: A precision approach to tumour treatment. Dienstmann R, Tabernero J. Nature. 2017;548(7665):40-41.
  10. Reply to the letter to the editor 'Including lynch syndrome in personalized prognostication and follow-up of stage II and III colon cancer' by Sciallero et al. Dienstmann R, Guinney J. Annals Oncol 2017;28(11):2889-2890.
  11. Colorectal cancer Consensus Molecular Subtypes translated to preclinical models uncover potentially targetable cancer-cell dependencies. Sveen A, Bruun J, Eide PW, Eilertsen IA, Ramirez L, Murumägi A, Arjama MA, Danielsen SA, Kryeziu K, Elez E, Tabernero J, Guinney J, Palmer HG, Nesbakken A, Kallioniemi O, Dienstmann R, Lothe RA. Clin Cancer Res. 2017 Dec 14. 
  12. Tumor side as model of integrative molecular classification of colorectal cancer. Dienstmann R. Clin Cancer Res. 2017 Dec 21.

PROJECTS

  • MERCK Grant for Oncology Innovation.
  • MedBioinformatics.
  • MoTriColor.
  • Variant Interpretation for Cancer Consortium.

AWARDS

  • Leaders Generation Program Award, European Society for Medical Oncology (ESMO).

Radiation Oncology Group

Imagen

Principal Investigator
Jordi Giralt

Radiation Oncologists
Manuel Altabas
Sergi Benavente
Alexandra Giraldo
Xavier Maldonado
Andrés Muñiz
Begoña Navaltropo
Mónica Ramos
Victoria Reyes
Ramona Verges

SUMMARY

Our group is integrated within the Radiation Oncology Department of the Vall d'Hebron University Hospital (HUVH), and is actively involved in the multidisciplinary treatment of patients with malignant tumors. We also participate either as principal investigators or research collaborators across a number of pioneering clinical trials, translational research projects, as well as technology development programs.

Current and future research priorities include the following key areas:

  • Development of an estereotactic extracranial radiotherapy program in pancreas and prostate.
  • The setting up of a 4D program for lung cancer.
  • In breast cancer, the validation of partial breast irradiation in prone position technique.
  • Establishing benefit of dose painting and adaptive radiotherapy in head and neck cancer in a clinical trial.
  • Analyzing the combination of PD-1 immunotherapy monoclonal antibodies with hypofractionated radiotherapy in metastasis and in locally advanced squamous cell carcinoma of the head and neck.
  • Dose escalation trials in prostate cancer using hypofractionation and IGRT.
Imagen

Figure: Dose distribution in a 4 years old child treated with cranio-spinal irradiation for a standard-risk medulloblastoma, using VMAT IMRT. A) Sagittal view at mid-line B) Sagittal view at eye's level C) Coronal view D) Cranial-sagittal view (in yellow the hippocampus, in blue the cochlea) E) Axial view (in yellow the hippocampus, in blue the hypophysis).

STRATEGIC GOALS

  • Technology development: acquisition of new equipment to implement cutting edge clinical treatment techniques such as rotational radiotherapy - with intensity modulated arc therapy (VMAT), adaptive radiotherapy, and image-guided radiotherapy (IGRT).
  • Translational research: application of insights into cancer biology as well as healthy tissue in order to personalize therapy matched to the characteristics and specificities of each patient, each individual tumor.

HIGHLIGHTS

  • An increase in the number of patients treated with IMRT and RC/SBRT. In 2017 we treated 815 patients with IMRT and 93 patients with RC/SBRT; representing an increase of 34% and 24%, respectively.
  • The Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE) project began in the year 2013. At present we have included 57 patients and are consequently the top recruiters in this collaboration.
  • We initiated a dose escalation program using Image Guided RadioTherapy (IGRT) with fiducials, and have since treated 21 patients.
  • New clinical studies in the treatment of prostate cancer with enzalutamide, and in lung/liver metastases with atezolizumab immunotherapy.

PI PAPER PICK (full list for 2017 below)

Mañós M, Giralt J, Rueda A, Cabrera J, Martinez-Trufero J, Marruecos J, et al. Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1). Oral Oncol. 2017 Jul;70:58-64.

Christiaens M, Collette S, Overgaard J, Gregoire V, Kazmierska J, Castadot P, Giralt J, Grant W, Tomsej M, Bar-Deroma R, Monti AF, Hurkmans CW, Weber DC. Quality assurance of radiotherapy in the ongoing EORTC 1219-DAHANCA-29 trial for HPV/p16 negative squamous cell carcinoma of the head and neck: Results of the benchmark case procedure. Radiother Oncol. 2017 Jun;123(3):424-430.

Bonner JA, Mesia R, Giralt J, Psyrri A, Keilholz U, Rosenthal DI, Beier F, Schulten J, Vermorken JB. p16, HPV, and Cetuximab: What Is the Evidence? Oncologist. 2017 Jul;22(7):811-822.

Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines. Grégoire V, Evans M, Le QT, Bourhis J, Budach V, Chen A, Eisbruch A, Feng M, Giralt J, Gupta T, Hamoir M, Helito JK, Hu C, Hunter K, Johansen J, Kaanders J, Laskar SG, Lee A, Maingon P, Mäkitie A, Micciche' F, Nicolai P, O'Sullivan B, Poitevin A, Porceddu S, Składowski K, Tribius S, Waldron J, Wee J, Yao M, Yom SS, Zimmermann F, Grau C. Radiother Oncol. 2018 Jan;126(1):3-24. Epub 2017 Nov 24.

HORIZONS 2018

  • The combination of PD-1 immunotherapy monoclonal antibodies with radiochemotherapy in locally advanced head and neck cancer.
  • Adaptive radiotherapy in gynecological tumors: plan of the day.
  • Development of a stereotactic body radiotherapy (SBRT) program in new areas; spinal and lymph nodes.
  • Set up a 4D program for lung cancer.
  • Implement the Image Guided RadioTherapy (IGRT) program for prostate and uterine cervix.
  • The use of nanoparticles as radiotherapy enhancement for soft tissue sarcomas.

PUBLICATIONS

  1. Rueda A, Giralt J, Mañós M, Lozano A, Sistiaga A, García-Miragall E, Cacicedo J, Esteban F, Scola B, Contreras J, Ruiz A, Carral A, Sanchez-Aniceto G, Pastor M, Herranz JJ, Bernal M, Mesía R. Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2). Oral Oncol. 2017 Jul;70:65-72. doi: 10.1016/j.oraloncology.2017.04.005.
  2. Mañós M, Giralt J, Rueda A, Cabrera J, Martinez-Trufero J, Marruecos J, Lopez-Pousa A, Rodrigo JP, Castelo B, Martínez-Galán J, Arias F, Chaves M, Herranz JJ, Arrazubi V, Baste N, Castro A, Mesía R. Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1). Oral Oncol. 2017 Jul;70:58-64. doi: 10.1016/j.oraloncology.2017.04.004.
  3. Alsina M, Rivera F, Ramos FJ, Galán M, López R, García-Alfonso P, Alés-Martinez JE, Queralt B, Antón A, Carrato A, Grávalos C, Méndez-Vidal MJ, López C, de Mena IR, Tabernero J, Giralt J, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and Grupo de Investigación Clínica en Oncología Radioterápica (GICOR). Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Target Oncol. 2017 Dec 14. doi: 10.1007/s11523-017-0544-z.
  4. Grégoire V, Evans M, Le QT, Bourhis J, Budach V, Chen A, Eisbruch A, Feng M, Giralt J, Gupta T, Hamoir M, Helito JK, Hu C, Hunter K, Johansen J, Kaanders J, Laskar SG, Lee A, Maingon P, Mäkitie A, Micciche' F, Nicolai P, O'Sullivan B, Poitevin A, Porceddu S, Składowski K, Tribius S, Waldron J, Wee J, Yao M, Yom SS, Zimmermann F, Grau C. Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines. Radiother Oncol. 2017 Nov 24. pii: S0167-8140(17)32656-7. doi: 10.1016/j.radonc.2017.10.016.
  5. Morote J, Comas I, Planas J, Maldonado X, Celma A, Placer J, Ferrer R, Carles J, Regis L. Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy. Clin Genitourin Cancer. 2017 Nov 30. pii: S1558-7673(17)30341-5. doi: 10.1016/j.clgc.2017.10.025.
  6. Casas F, Henríquez I, Bejar A, Maldonado X, Alvarez A, González-Sansegundo C, Boladeras A, Ferrer F, Hervás A, Herruzo I, Caro M, Rodriguez I, Ferrer C. Intermittent versus continuous androgen deprivation therapy to biochemical recurrence after external beam radiotherapy: a phase 3 GICOR study. Clin Transl Oncol. 2017 Mar;19(3):373-378. doi: 10.1007/s12094-016-1538-5.
  7. Martínez-Garcia M, Álvarez-Linera J, Carrato C, Ley L, Luque R, Maldonado X, Martínez-Aguillo M, Navarro LM, Vaz-Salgado MA, Gil-Gil M. SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017). Clin Transl Oncol. 2017 Oct 30. doi:10.1007/s12094-017-1763-6.
  8. Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martinez-Ricarte F, Rodon J, Auger C, Aizpurua M, Salas-Puig J, Santamarina E, Martinez-Saez E. Epileptic features and survival in glioblastomas presenting with seizures. Epilepsy Res. 2017 Feb;130:1-6.doi:10.1016/j.eplepsyres.2016.12.013.
  9. Giraldo A, Benavente S, Ramos M, Vergés R, Coronil O, Arbeláez L, Maldonado X, Altabas M, Mollà M, Reyes V, Navalpotro B, Giralt J. Effectiveness of radiotherapy for metastatic spinal cord compression in patients with short life expectancy. Rep Pract Oncol Radiother. 2017 Jan-Feb;22(1):58-63.
  10. Regis L, Planas J, Carles J, Maldonado X, Comas I, Ferrer R, Morote J. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone. 2017 Jan;77(1):114-120. doi: 10.1002/pros.23256.
  11. Alsina M, Rivera F, Ramos FJ, Galán M, López R, García-Alfonso P, Alés-Martinez JE, Queralt B, Antón A, Carrato A, Grávalos C, Méndez-Vidal MJ, López C, de Mena IR, Tabernero J, Giralt J, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and Grupo de Investigación Clínica en Oncología Radioterápica (GICOR). A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Target Oncol. 2017 Nov 11. doi: 10.1007/s11523-017-0536-z.
  12. Cambra MJ, Farrús B, Moreno F, Anglada L, Arenas M, Ballester R, Casals J, Cusidó M, García V, Gutiérrez C, Mollà M, Pedro A, Reyes V, Sanz X. Management of breast ductal carcinoma in situ in Catalonia, Spain: Results from the Grup Oncologic Calalà-Occità-Catalonia survey with 9-year follow up. Breast. 2017 Oct;35:196-202. doi: 10.1016/j.breast.2017.08.002.
  13. Christiaens M, Collette S, Overgaard J, Gregoire V, Kazmierska J, Castadot P, Giralt J, Grant W, Tomsej M, Bar-Deroma R, Monti AF, Hurkmans CW, Weber DC. Quality assurance of radiotherapy in the ongoing EORTC 1219-DAHANCA-29 trial for HPV/p16 negative squamous cell carcinoma of the head and neck: Results of the benchmark case procedure. Radiother Oncol. 2017 Jun;123(3):424-430. doi: 10.1016/j.radonc.2017.04.019.
  14. Prades J, Algara M, Espinàs JA, Farrús B, Arenas M, Reyes V, García-Reglero V, Cambra MJ, Rubio E, Anglada L, Eraso A, Pedro A, Fuentes-Raspall MJ, Tuset V, Solà J, Borras JM. Understanding variations in the use of hypofractionated radiotherapy and its specific indications for breast cancer: A mixed-methods study. Radiother Oncol. 2017 Apr;123(1):22-28. doi: 10.1016/j.radonc.2017.01.014.
  15. Janssens GO, Gandola L, Bolle S, Mandeville H, Ramos-Albiac M, van Beek K, Benghiat H, Hoeben B, Morales La Madrid A, Kortmann RD, Hargrave D, Menten J, Pecori E, Biassoni V, von Bueren AO, van Vuurden DG, Massimino M, Sturm D, Peters M, Kramm CM. Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group. Eur J Cancer. 2017 Mar;73:38-47. doi: 10.1016/j.ejca.2016.12.007.
  16. Gutiérrez Santamaría J, Masiá Gridilla J, Pamias Romero J, Giralt López-de-Sagredo J, Bescós Atín MS. Fat grafting is a feasible technique for the sequelae of head and neck cancer treatment. J Craniomaxillofac Surg. 2017 Jan;45(1):93-98. doi: 10.1016/j.jcms.2016.10.019.
  17. Bonner JA, Mesia R, Giralt J, Psyrri A, Keilholz U, Rosenthal DI, Beier F, Schulten J, Vermorken JB.p16, HPV, and Cetuximab: What Is the Evidence? Oncologist. 2017 Jul;22(7):811-822. doi: 10.1634/theoncologist.2016-0433.
  18. Barrera-Ochoa S, Gallardo-Calero I, Sallent A, López-Fernández A, Vergés R, Giralt J, Aguirre-Canyadell M, Velez R. New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research. Lab Anim. 2017 Apr;51(2):124-137. doi: 10.1177/0023677216656221. Epub 2016 Jul 9.

PROJECTS

Funded Projects

  • Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE).
  • Supported through a European grant of the EU 7th Framework Programme (FP7), this project aims to optimize the delivery of (chemo) radiotherapy and/or surgery to cancer patients. Participating centers: The Netherlands Cancer Institute, Karolinska Institutet, Institut Gustave Roussy, Maastro Clinic, the Vall d’Hebron University Hospital, Christie Hospital, European Society for Radiotherapy & Oncology (ESTRO), Maastro innovations, and RaySearch. This study explores dose escalation strategies using adaptive radiotherapy and metabolic and biological markers. We participate in the study of patients with head and neck tumors.
  • adiogenomics Biorepository and Databank (RBD) PAR-11-167 Core Infrastructure and Methodological Research for Cancer Epidemiology Cohorts (UM1).
  • In addition to DNA isolated from blood collected epidemiological data / records of patient outcomes related to the treatment.
  • The main aim will be normal tissue toxicity data from patients and electronic data capture. A unique element of this project is the centralized storage of radiotherapy treatment plans.
  • Evaluation of the efficacy and effectiveness of new treatments for localized prostate cancer at low risk (FIS)
  • A multicenter randomized trial in patients diagnosed with low-risk prostate cancer controlled clinical trial design. Patients will be treated with laparoscopic radical prostatectomy, robotic surgery, brachytherapy or IMRT. Main endpoints are performance parameters and quality of life. To evaluate the probability of nonadherence to external radiotherapy and its associated factors in patients treated for cancer in Catalonia (FIS).
  • Patient non adherence to external radiotherapy and the frequency of retreatment are two parameters with very few studies available. There are currently none from a population based perspective. Retreatments are increasing due to the improvements in technology and progression in survival. Both are key factors in the planning of radiotherapy planning resources.
  • This project has two complementary objectives: 1. to analyze the probability of non adherence to external radiotherapy treatment, its associated factors and its association with one year survival; and 2. assess the frequency of retreatments during the five years following initial therapy for the same primary tumor, and its relationship with the tumor site, intention for treatment and time from the initial therapy.

Non Funded Projects

  • Adaptive radiation therapy based on PET functional imaging for H&N cancer patients
  • Breast irradiation, comparisons and analysis of dose distribution and reproducibility in supine versus prone position.
  • Phase II clinical Essay extracranial stereotactic radiotherapy in the treatment of locally advanced prostate cancer.
  • Instrumentation radiotherapy of the spine and paraspinal tumors and metastases.
  • Extracranial stereotactic radiotherapy in pancreatic cancer, commissioning and validation of the technique.
  • Techniques for reducing toxicity: radiotherapy treatment in the pediatric patients with brain tumors.
  • Radiation treatment planning of gynecological tumors. Monitoring compliance in filling the urinary bladder.
  • Total marrow irradiation program for bone marrow transplantation in patients with multiple myeloma; dosimetric studies.
  • A feasibility trial evaluating anti-PD1 nivolumab consolidation after standard first-line chemotherapy and radiotherapy in locally advanced stage IIIA/B NSCLC.
  • REQUITE project. Inclusion and monitoring of lung cancer patients.
  • Adaptive radiotherapy in the treatment of patients with non-small cell lung neoplasia in stages IIA and IIB.(AG) 288/216.
  • Extracranial stereotactic radiotherapy (SBRT) as a treatment for unresectable liver metastases.

AWARDS

  • ISO 9001 (2015) accreditation.

Thoracic Tumors & Head and Neck Cancer Group

Imagen

Principal Investigator
Enriqueta Felip

Medical Oncologists
Neus Basté
Irene Braña
Susana Cedrés
Alex Martínez
Ana Maria Martínez
Alejandro Navarro
Nuria Pardo
Jordi Remon

Clinical Nurse Specialists
Carlos Justicia
Gisela Rodriguez

SUMMARY

VHIO's Thoracic Tumors & Head and Neck Cancer Group tackles the challenges posed by thoracic malignancies, including lung cancer, mesothelioma and thymic malignancies, and head and neck cancers. We concentrate on disease prevention, early detection and more precise techniques in diagnosis and staging towards advancing personalized medicine in oncology. Our group also focuses on targeted therapies in patients with specific molecular alterations, and is dedicated to both unmasking molecular mechanisms of acquired resistance and optimizing novel immunotherapy strategies.

For our patients with early-stage thoracic malignancies, we liaise closely with a multidisciplinary team incorporating thoracic surgeons, radiation therapists, radiologists, pulmonologists and pathologists, in order to optimize various treatment approaches and modalities. Given that these individuals can suffer from severe symptoms we strive to ameliorate patient outcomes by working in tight connectivity with professionals from other disciplines.

Personalized therapy for patients with advanced lung cancer is now the standard approach. We therefore aim to widely establish molecular determinants to better match therapies to the specificities of individual patients, not only in tumors but also in circulating-free DNA (liquid biopsy).

Novel immunotherapy strategies have a role in the treatment algorithm for the management of lung cancer; a number of protocols are now ongoing in our unit. We actively contribute to VHIO's early clinical drug development efforts, led by Elena Garralda, and also manage other less common thoracic malignancies including small-cell lung cancer, mesothelioma, thymoma and neuroendocrine tumors.

For patients with head and neck tumors we work in close collaboration with expert surgeons, radiotherapists, radiologists, pathologists, and nutritionists, and also lead a clinical trial program analyzing immunotherapeutic approaches and targeted agents in this particular setting.

Imagen

Figure: Martinez-Martí A, et al. Ann Oncol. 2017. The figure shows experiments performed in a PDX model from a metastatic brain biopsy at the time of progression to osimertinib. The results showed differential treatment response to a drug combination (d) and clonal evolution of tumor (e and f).

STRATEGIC GOALS

  • Contribute to early drug development and targeted therapies for thoracic and head and neck tumors.
  • Advance personalized medicine for lung cancer patients through translational research and the application of cutting-edge technologies and novel approaches.
  • Potentiate new therapies including immunotherapeutics and targeted agents for the management of patients with thoracic and head and neck malignancies.
  • Further strengthen multidisciplinarity to provide optimal care for our patients.

HIGHLIGHTS

  • 500 new lung cancer patients including 20 cases of mesothelioma and 5 thymoma.
  • 250 new head and neck cancer patients.
  • We continue to foster multidisciplinarity through our Thoracic Tumors Committee that convenes twice a week.
  • Our head and neck cancer patients are discussed by a multidisciplinary team, twice a week.
  • Implementation of pharmacogenomic approaches in advanced lung cancer in collaboration with VHIO's Cancer Genomics Group led by Ana Vivancos, and the Vall d'Hebron University Hospital Pathology Service, working with Javier Hernández and Irene Sansano.
  • Implementation of liquid biopsy for certain patients with advanced NSCLC.
  • Our group has collaborated in the development of a number of drugs in lung cancer matched to specific molecular alterations. As a result of these studies some of these agents have already been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
  • We have successfully led two translational projects resulting in the publication of scientific articles: one reporting on the tumor heterogeneity and treatment response of a EGFR-mutated lung cancer patient (Martinez-Martí A et al. Ann Oncol. 2017), and the second, establishing immune-related expression profiles in NSCLC and head and neck tumors (Navarro A et al. Cancer Res. 2017)
  • Development of immune-based strategies in thoracic and head and neck malignancies.

PI PAPER PICK (full list for 2017 below)

Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599.

Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel JM, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer HG, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457.

Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh CK, Rizvi NA, Chaft JE, Carcereny Costa E, Patel JD, Chow LQM, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH). J Clin Oncol. 2017 Aug 20;35(24):2781-2789

Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised , controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886.

HORIZONS 2018

  • Potentiate and expand our international collaborations.
  • Consolidate our translational research program in thoracic malignancies.
  • Expand our research scope to include uncommon molecular subgroups and tumor types.
  • Further develop the use of liquid biopsy in baseline testing and patient follow-up.

PUBLICATIONS

  1. Gridelli C, Baas P, Barlesi F, Ciardiello F, Crinò L, Felip E, Gadgeel S, Papadimitrakopoulou V, Paz-Ares L, Planchard D, Perol M, Hanna N, Sgambato A, Casaluce F, de Marinis F. Second-Line Treatment Options in Non-Small-Cell Lung Cancer: Report From an International Experts Panel Meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2017 Dec 22. pii: S1525-7304(17)30349-2.
  2. Navarro A, Felip E. Pembrolizumab in advanced pretreated small cell lung cancer patients with PD-L1 expression: data from the KEYNOTE-028 trial: a reason for hope? Transl Lung Cancer Res. 2017 Dec;6(Suppl 1):S78-S83.
  3. Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two Phase II trials. Ann Oncol. 2017 Dec 23.
  4. Felip E, Barlesi F, Besse B, Chu Q, Gandhi L, Kim SW, Carcereny E, Sequist LV, Brunsvig P, Chouaid C, Smit EF, Groen HJM, Kim DW, Park K, Avsar E, Szpakowski S, Akimov M, Garon EB. Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2017 Dec 13. pii: S1556-0864(17)33083-6.
  5. Letovanec I, Finn S, Zygoura P, Smyth P, Soltermann A, Bubendorf L, Speel EJ, Marchetti A, Nonaka D, Monkhorst K, Hager H, Martorell M, Sejda A, Cheney R, Hernandez-Losa J, Verbeken E, Weder W, Savic S, Di Lorito A, Navarro A, Felip E, Warth A, Baas P, Meldgaard P, Blackhall F, Dingemans AM, Dienemann H, Dziadziuszko R, Vansteenkiste J, O'Brien C, Geiger T, Sherlock J, Schageman J, Dafni U, Kammler R, Kerr K, Thunnissen E, Stahel R, Peters S; European Thoracic Oncology Platform Lungscape Consortium. Evaluation of NGS and RT-PCR Methods for ALK Rearrangement in European NSCLC Patients: Results from the European Thoracic Oncology Platform Lungscape Project. J Thorac Oncol. 2017 Nov 27. pii: S1556-0864(17)33063-0
  6. Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599
  7. Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhäeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crinò L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec 10;35(35):3924-3933.
  8. Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel JM, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer HG, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457.
  9. Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247
  10. Jacobsen K, Bertran-Alamillo J, Molina MA, Teixidó C, Karachaliou N, Pedersen MH, Castellví J, Garzón M, Codony-Servat C, Codony-Servat J, Giménez-Capitán A, Drozdowskyj A, Viteri S, Larsen MR, Lassen U, Felip E, Bivona TG, Ditzel HJ, Rosell R. Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer. Nat Commun. 2017 Sep 4;8(1):410.
  11. Felip E, Hirsh V, Popat S, Cobo M, Fülöp A, Dayen C, Trigo JM, Gregg R, Waller CF, Soria JC, Goss GD, Gordon J, Wang B, Palmer M, Ehrnrooth E, Gadgeel SM. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy. Clin Lung Cancer. 2018 Jan;19(1):74-83.e11.
  12. Remon J, Isla D, Garrido P, de Castro J, Majem M, Viñolas N, Artal A, Carcereny E, García-Campelo MR, Lianes P, Provencio M, Juan O, Diz P, Blanco R, Lopez-Castro R, Maestu I, Vadell C, Felip E. Efficacy of tyrosine kinase inhibitors in EGFR-mutant lung cancer women in a real-world setting: the WORLD07 database. Clin Transl Oncol. 2017 Dec;19(12):1537-1542
  13. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426.
  14. Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh CK, Rizvi NA, Chaft JE, Carcereny Costa E, Patel JD, Chow LQM, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH). J Clin Oncol. 2017 Aug 20;35(24):2781-2789.
  15. Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886.
  16. Meulendijks D, Jacob W, Voest EE, Mau-Sorensen M, Martinez-Garcia M, Taus A, Fleitas T, Cervantes A, Lolkema MP, Langenberg MHG, De Jonge MJ, Sleijfer S, Han JY, Calles A, Felip E, Kim SW, Schellens JHM, Wilson S, Thomas M, Ceppi M, Meneses-Lorente G, James I, Vega-Harring S, Dua R, Nguyen M, Steiner L, Adessi C, Michielin F, Bossenmaier B, Weisser M, Lassen UN. Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity. Clin Cancer Res. 2017 Sep 15;23(18):5406-5415.
  17. Gadgeel S, Goss G, Soria JC, Felip E, Georgoulias V, Lu S, Cobo M, Syrigos K, Lee KH, Göker E, Guclu SZ, Isla D, Morabito A, Dupuis N, Bühnemann C, Krämer N, Solca F, Ehrnrooth E, Ardizzoni A. Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study. Lung Cancer. 2017 Jul;109:101-108.
  18. Prat A, Navarro A, Paré L, Reguart N, Galván P, Pascual T, Martínez A, Nuciforo P, Comerma L, Alos L, Pardo N, Cedrés S, Fan C, Parker JS, Gaba L, Victoria I, Viñolas N, Vivancos A, Arance A, Felip E. Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma. Cancer Res. 2017 Jul 1;77(13):3540-3550.
  19. Mok TSK, Crino L, Felip E, Salgia R, De Pas T, Tan DSW, Chow LQM. The accelerated path of ceritinib: Translating pre-clinical development into clinical efficacy. Cancer Treat Rev. 2017 Apr;55:181-189.
  20. Rosell R, Dafni U, Felip E, Curioni-Fontecedro A, Gautschi O, Peters S, Massutí B, Palmero R, Aix SP, Carcereny E, Früh M, Pless M, Popat S, Kotsakis A, Cuffe S, Bidoli P, Favaretto A, Froesch P, Reguart N, Puente J, Coate L, Barlesi F, Rauch D, Thomas M, Camps C, Gómez-Codina J, Majem M, Porta R, Shah R, Hanrahan E, Kammler R, Ruepp B, Rabaglio M, Kassapian M, Karachaliou N, Tam R, Shames DS, Molina-Vila MA, Stahel RA; BELIEF collaborative group. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2017 May;5(5):435-444.
  21. Viñolas N, Garrido P, Isla D, Provencio M, Majem M, Artal A, Carcereny E, Garcia Campelo R, Lianes P, De La Peñas R, Felip E. Lung Cancer in Never-Smoking Women: A Sub-Analysis of the Spanish Female-Specific Database WORLD07. Cancer Invest. 2017 May 28;35(5):358-365.
  22. Pereira C, Gimenez-Xavier P, Pros E, Pajares MJ, Moro M, Gomez A, Navarro A, Condom E, Moran S, Gomez-Lopez G, Graña O, Rubio-Camarillo M, Martinez-Martí A, Yokota J, Carretero J, Galbis JM, Nadal E, Pisano D, Sozzi G, Felip E, Montuenga LM, Roz L, Villanueva A, Sanchez-Cespedes M. Genomic Profiling of Patient-Derived Xenografts for Lung Cancer Identifies B2M Inactivation Impairing Immunorecognition. Clin Cancer Res. 2017 Jun 15;23(12):3203-3213.
  23. Remon J, Pardo N, Martinez-Martí A, Cedrés S, Navarro A, Martinez de Castro AM, Felip E. Immune-checkpoint inhibition in first-line treatment of advanced non-small cell lung cancer patients: Current status and future approaches. Lung Cancer. 2017 Apr;106:70-75. doi: 10.1016/j.lungcan.2017.02.002. Epub 2017 Feb 6. Review
  24. Guillaumet-Adkins A, Rodríguez-Esteban G, Mereu E, Mendez-Lago M, Jaitin DA, Villanueva A, Vidal A, Martinez-Marti A, Felip E, Vivancos A, Keren-Shaul H, Heath S, Gut M, Amit I, Gut I, Heyn H. Single-cell transcriptome conservation in cryopreserved cells and tissues. Genome Biol. 2017 Mar 1;18(1):45.
  25. Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, Blackhall F, Haggstrom D, Yoh K, Novello S, Gold K, Hirashima T, Lin CC, Mann H, Cantarini M, Ghiorghiu S, Jänne PA. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol. 2017 Apr 20;35(12):1288-1296.
  26. Hui R, Garon EB, Goldman JW, Leighl NB, Hellmann MD, Patnaik A, Gandhi L, Eder JP, Ahn MJ, Horn L, Felip E, Carcereny E, Rangwala R, Lubiniecki GM, Zhang J, Emancipator K, Roach C, Rizvi NA. Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial. Ann Oncol. 2017 Apr 1;28(4):874-881.
  27. Rivera F, Andres R, Felip E, Garcia-Campelo R, Lianes P, Llombart A, Piera JM, Puente J, Rodriguez CA, Vera R, Virizuela JA, Martin M, Garrido P. Medical oncology future plan of the Spanish Society of Medical Oncology: challenges and future needs of the Spanish oncologists. Clin Transl Oncol. 2017 Apr;19(4):508-518
  28. Isla D, Majem M, Viñolas N, Artal A, Blasco A, Felip E, Garrido P, Remón J, Baquedano M, Borrás JM, Die Trill M, García-Campelo R, Juan O, León C, Lianes P, López-Ríos F, Molins L, Planchuelo MÁ, Cobo M, Paz-Ares L, Trigo JM, de Castro J. A consensus statement on the gender perspective in lung cancer. Clin Transl Oncol. 2017 May;19(5):527-535.
  29. Manegold C, Dingemans AC, Gray JE, Nakagawa K, Nicolson M, Peters S, Reck M, Wu YL, Brustugun OT, Crinò L, Felip E, Fennell D, Garrido P, Huber RM, Marabelle A, Moniuszko M, Mornex F, Novello S, Papotti M, Pérol M, Smit EF, Syrigos K, van Meerbeeck JP, van Zandwijk N, Chih-Hsin Yang J, Zhou C, Vokes E. The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC. J Thorac Oncol. 2017 Feb;12(2):194-207.

PROJECTS

  • Grantor: AECC Scientific Foundation
    Ref.: GCB14-2170
    Title: Use of next-generation sequencing technologies for the identification of new therapeutic targets and prognostic markers in lung carcinoma poorly characterized.
    Coordinator: Luis Montuenga – CIMA (University of Navarra)
    Partner 3: Vall d’Hebron Institute of Oncology (VHIO)
    Principal Investigator: Enriqueta Felip
    2014 – 2019
  • Grantor: Instituto de Salud Carlos III
    Ref.: PI14/01248
    Title: Wnt/Beta-Catenin inhibitors as promising therapy for NSCLC treatment.
    2014 - 2017
  • Grantor: Grant for Oncology Innovation - Merck
    Title: New technologies for new treatments: liquid biopsy meets immunotheraphy.
    2014 - 2018
  • Grantor: Instituto de Salud Carlos III
    Ref.: PI17/00938
    Title: Wnt/beta-catenin pathway activation in advanced non-small cell lung cancer: implications in resistance to immunotherapy and novel therapeutic strategies.
    2018 - 2020
  • Grantor:ERA-NET Transcan 2017
    Ref.:TRANSCAN-084
    Title: Non-invasive prognostic markers for Resected Early-STage NSCLC: role of circulatING and exosomal miRNAs and free circulating DNA (RESTING).
    Coordinator: Paola Ulivi– IRST-IRCCS
    Partner 2: Vall d’Hebron Institute of Oncology (VHIO)
    Principal Investigator: Enriqueta Felip
    2018 - 2020

AWARDS

  • Voted in by its members in 2017, Enriqueta serves on the Board of Directors of the International Association for the Study of Lung Cancer (IASLC). She imparts her expertise in lung cancer and other thoracic malignancies and assumes a key role in effectively enhancing the development of existing IASLC programs and committees set firmly within the context of precision medicine.
  • Our Group has been recognized as a Consolidated Research Group by AGAUR-SGR.