PROGRAMS & GROUPS

PLEASE CLICK ON THE CORRESPONDING PROGRAMS BELOW

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Josep Tabernero

Clinical Research Director
"Our Program, incorporating multidisciplinary cancer teams, develops novel agents and approaches to diagnose cancer earlier and better predict response to therapy. Pioneering studies involving both preclinical and early-drug development discovery, we also lead several clinical trials designed to render anti-cancer therapies more precise."

Click here to read our Program Director´s synopsis 2015

Our multidisciplinary and translational approach to clinical research closely connects VHIO scientists with our physician-researchers and in so doing, enables VHIO’s Clinical Research Program to spearhead cooperative preclinical, Phase I & II studies aimed at developing novel therapeutics, as well as new or redefined prognostic/diagnostic tools to better detect disease and more precisely predict response to anti-cancer therapies.

Throughout 2015 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, through our collaboration with Merck Serono and Sysmex Inostics, we have been using our in-house BEAMing digital PCR/flow cytometry technology to evaluate patients with metastatic colorectal cancer. We have already reported promising findings from a large, multi-center phase III trial – the CORRECT study. These results, published in The Lancet Oncology, are illustrative of a body of compelling research positioning liquid biopsy as the future of cancer detection and an essential tool in clinical practice. Importantly, as this Scientific Report goes to print, this RAS biomarker test has just received European Conformity approval (CE Mark), which makes it available and accessible for patients in Europe, Asia, and Australia.

In addition to this potentially game changing approach, cancer immunotherapy also represents a firm contender in dismantling cancer’s armory and is as exciting for our preclinical scientists as it is for our clinical researchers. This year, out of VHIO Thoracic Tumors Group’s impressive trio of 2015 New England Journal of Medicine papers, in collaboration with our Early Clinical Drug Development Group, two indicated new hope for lung cancer patients based on novel immunological strategies. As we are starting to see the benefit of immunotherapeutics across several clinical studies, immuno-oncology could well be poised to impact the way we will treat cancer in the future. I can predict that our Program, in collaboration with other VHIO groups and colleagues from other leading cancer research centers across Europe and beyond, will continue to both evidence and advance the use of novel immune agents either as mono therapy or in combination, across an increasing number of cancer types.

Joining our important portfolio of clinical trials, we are now leading and implementing a number of new Basket trials. One such study, actually the very first of them, was a broad phase II trial that evidenced the potential of a BRAF inhibitor, already effective in the treatment of melanoma, as anti-cancer therapy for other malignancies. This discovery, co-led by Memorial Sloan Kettering Cancer Center (MSKCC) and VHIO, was published in NEJM in 2015.

We are also collaborating in the development of molecular tests for patient screening (disease-oriented mutation panels for NGS platforms and Nanostring nCounter), led by VHIO’s Cancer Genomics Group. Driving our efforts aimed at integrating clinical translational research with genomics for precision cancer therapy, VHIO’s recently incorporated Oncology Data Science (ODysSey), has made important progress in the datamining, molecular profiling and sub-typing of different cancers. Research in 2015 contributed to both establishing and achieving consensus on newly defined molecular subtypes of colorectal cancer, as published in Nature Medicine.

It is thanks to the excellence and expertise of all our clinical groups, in collaboration with other VHIO programs, that results from our early phase trials and translational investigations, have also resulted in publications in many other top-tier journals including: Nature, The Lancet Oncology, Cancer Cell, Cancer Discovery, and the Journal of Clinical Oncology (Click here for the full listing of articles published by VHIO investigators in 2015).

Just as VHIO continues to significantly advance cancer discovery and therapeutics to ultimately benefit an increasing number of patients, it must continue to progress in partnership, across borders. In addition to our continued participation in existing consortia of excellence, I am pleased to announce the launch of the MoTriColor consortium, led by VHIO, as well the MedBioinformatics project -- both of which are backed by Horizon 2020 funding.

Lastly but by no means least, I believe in forging closer collaborations with other specialties and key partners in oncology including pharmaceutical companies and policymakers. Only then will we collectively better serve the most deserved stakeholders of all -- our patients.

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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Jordi Rodón
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 / Cristina Saura

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Principal Investigator
Cristina Saura

Associate Translational Investigator
Javier Cortés

Medical Oncologists and Clinical Fellows
Judith Balmaña
Meritxell Bellet
Patricia Gómez
Eva Muñoz
Mafalda Oliveira

Vanesa Ortega
José Manuel Pérez
Jesús Soberino
Mª Jesús Vidal
Esther Zamora

Summary / Breast Cancer & Melanoma Group

Our Breast Cancer Program continues to be one of the most active in Spain and one of the most renowned across Europe. In 2015, 32 publications (18 of them in the first quartile), totaled an Impact Factor (IF) of 383,45 with a mean IF of 11,98. Interestingly, we published two articles in the New England Journal of Medicine this year, a highly prestigious publication renowned for publishing practice changing data in biomedicine. In both studies, VHIO’s authors were also involved in the design of the respective trials.

This year we have initiated more than 15 new clinical trials and studies. Our group is not only committed to participating in clinical and preclinical studies, but also leads several of them -- reflected by our representation of Steering Committees for some, and appointed international leaders for others.

Our main areas of interest continue to center on the development of novel therapies and the search for mechanisms of resistance to current agents. Multidisciplinary collaboration with surgeons, pathologists, radiologists and radiotherapists, among other disciplines, facilitates the incorporation of the most innovative treatments in clinical practice and optimizes therapeutic alternatives. In clinical research, our key areas of activity include:

  1. HER-positive breast tumors. We are particularly proud to have led some of the most important trials with pertuzumab. These studies have clearly resulting in improved survival of our patients and led to the full approval of this monoclonal antibody obtained throughout 2015. The dramatic results reported by our group represent the best to-date in the history of metastatic breast cancer.
  2. There are two compounds which are currently being tested in Phase II-III trials; Neratinib and TDM-1.We are now leading the NALA Trial – a pivotal phase III trial which compares neratinib plus capecitabine vs. the standard lapatinib plus capecitabine. We are also leading the only two studies to combine TDM1 with different chemotherapeutic agents, including capecitabine and liposomal doxorubicin. Interestingly, through our trials we have been able to attract new and promising molecules against HER2 including MM-302 and margetuximab. In close collaboration with VHIO´s Growth Factors Group, led by Joaquín Arribas, different mechanisms of resistance to these therapies are currently under study with particular interest in the design of new approaches to overlap these mechanisms.
  3. The optimization of chemotherapy-based strategies. The majority, if not all, of our patients with metastatic breast cancer will at some point require treatment with chemotherapy, and, unfortunately, they will ultimately develop resistance. For this reason, we strongly believe that overcoming mechanisms of resistance to chemotherapy will enhance the efficacy of these drugs. In collaboration with VHIO´s Experimental Therapeutics Group, led by Violeta Serra, we have demonstrated that the efficacy of eribulin depends on PI3K status and that resistance might be overcome by the addition of different PI3K inhibitors. The first patient will be treated with this combination in a Phase Ib/II trial in 2016.
  4. Application of new biological agents to reverse mechanisms of resistance to endocrine therapy. We are leading different early trials combining different approaches and using the most novel compounds in the field of PI3K-AKT-mTOR inhibitors and CDK4/6 inhibitors. Interestingly, through our participation in a Basket trial with Neratinib, we have already seen encouraging clinical activity for HR+ HER2- tumors harboring HER2 mutations.
  5. Triple Negative Breast Cancer. We are dedicated to leading this field of research over the next 4-5 years. We already have an extensive portfolio of clinical trials and preclinical projects aimed mainly at evaluating the potency of immunotherapy in this tumor type, and PARP inhibitors in patients with BRCA1/2 mutations.
  6. We collaborate closely with VHIO´s Early Clinical Drug Development Group headed by Jordi Rodón. This allows us to consider drugs that have been validated in very early studies and shown sufficient activity to expand these studies in patients with breast cancer. In 2015, we have developed clinical trials based on the preliminary efficacy results observed in early clinical trials. Our collaboration has also led to an increased enrollment of our breast cancer patients in early clinical trials.
  7. In collaboration with VHIO´s Cancer Genomics Group, led by Ana Vivancos, we are involved in exploring genes that mediate breast cancer metastasis to leptomeninges, and we are also working on another project to more effectively and deeply characterise the alterations that have emerged over time in the development of metastatic breast cancer. Analysing tumor tissue and cfDNA using highly sensitive techniques will ultimately enable us to identify new potential targets to be used in the development of future clinical trials.
  8. Our emerging Melanoma Group headed by Eva Muñoz, has made significant progress throughout 2015. We have doubled the number of patients treated within a clinical trial using novel molecules and have set up a translational melanoma research group at the Vall d'Hebron University Hospital (HUVH) in order to closely connect our scientists and physician-researchers. This collaboration has led to studies published in top-tier journals including Nature Genetics and Nature Medicine.

Strategic Goals / Breast Cancer & Melanoma Group

  1. Optimize treatment options for patients with breast cancer with particular focus on novel targeted agents which overcome resistance to standard anti-HER2 agents, chemotherapy and endocrine therapies.
  2. Render medicine more precise through insights gained into alterations found in tumor samples and cfDNA along the natural course of metastatic breast cancer.
  3. Continue to lead early clinical trials and closely collaborate with VHIO’s Preclinical Groups and swiftly transition to ´smarter´ studies based on solid data obtained from preclinical research and early drug development.
  4. Continue to lead the melanoma field in Spain -- not only as a reference center for treating melanoma patients with the very latest combinations available, but also as an emerging research group.

Highlights 2015 / Breast Cancer & Melanoma Group

  1. We have published practice-changing data in the field of adjuvant and metastatic breast cancer, leading to the approval of drugs such as pertuzumab and eribulin and increased therapeutic avenues for anti-hormonal treatment in premenopausal women in the adjuvant setting.
  2. We have been appointed to serve on the steering committees of some of the most relevant randomized Phase II and III clinical trials, and participated in some of the major clinical studies. One of our key goals is to be closely involved in the majority of drug trials subsequently leading to their approval for the treatment of breast cancer.
  3. We continued to develop patient-derived xenografts in close collaboration with the VHIO´s Preclinical Research Program, and currently have the most important collection of these models at European level.
  4. Thanks to the tremendous collaboration with surgeons, pathologists, other oncology professionals, and clinical departments at the Vall d´Hebron University Hospital (HUVH), our group has established itself as the most active in neoadjuvant studies in Spain.
  5. We developed our cell-free circulating tumour DNA program for genotyping and characterization in 2012. We have already published our first manuscript in this area.

PI Paper Pick / Breast Cancer & Melanoma Group

Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-734.

Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436-446.

De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C,Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Cajal SR, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015;6:8839.

Lin L; Sabnis AJ; Chan E; Olivas V; Cade L; Pazarentzos E; Asthana S; Neel D; Yan JJ; Lu X; Pham L; Wang MM; Karachaliou N; Cao MG; Manzano JL; Ramirez JL; Torres JM; Buttitta F; Rudin CM; Collisson EA; Algazi A; Robinson E; Osman I; Muñoz E; Cortes J; Frederick DT; Cooper ZA; McMahon M; Marchetti A; Rosell R; Flaherty KT; Wargo JA; Bivona TG. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat Genet. 2015;47(3):250-256.

Horizons 2016 / Breast Cancer & Melanoma Group

  1. Treat patients in our Phase I trial with eribulin and PI3K inhibitors.
  2. To correlate cfDNA with heterogeneity in breast cancer.
  3. Optimize clinical and preclinical research based on patient-derived xenografts.
  4. To study heterogeneity in breast tumors based on the neoadjuvant model.
  5. Lead novel and ´smarter´ clinical trials with special focus on targeted agents.
  6. Consolidate strategic alliances with the most prestigious European centers to work on independent clinical and preclinical studies.
  7. Achieve a better understanding on how chemotherapy affects the fetus in pregnant patients.
  8. Better understand tumor immunology in breast cancer.

Publications / Breast Cancer & Melanoma Group

  1. A first-in-human phase I, dose-escalation, multicentre study of HSP990 administered orally in adult patients with advanced solid malignancies. Spreafico A, Delord JP, De Mattos-Arruda L, Berge Y, Rodon J, Cottura E, Bedard PL, Akimov M, Lu H, Pain S, Kaag A, Siu LL, Cortes J. Br J Cancer. 2015 Feb 17;112(4):650-9.
  2. The expanding role of pertuzumab in the treatment of HER2-positive breast cancer. Moya-Horno I, Cortés J. Breast Cancer (Dove Med Press). 2015 May 21;7:125-32.
  3. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel intrastuzumab-refractory HER2-positive metastatic breast cancer. Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Breast Cancer Res Treat. 2015 Jan;149(1):151-61.
  4. Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-lable randomized phase 3 trial. Cortes J, Hudgens S, Twelves C, Perez EA, Awada A, Yelle L, McCutcheon S, Kaufman PA, Forsythe A, Velikova G. Breast Cancer Res Treat. 2015 Dec;154(3):509-20.
  5. Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. André F, Cortés J. Breast Cancer Res Treat. 2015 Feb;150(1):1-8.
  6. Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor. Blackwell K, Burris H, Gomez P, Lynn Henry N, Isakoff S, Campana F, Gao L, Jiang J, Macé S, Tolaney SM. Breast Cancer Res Treat. 2015 Nov;154(2):287-97.
  7. Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study. . Gil-Gil MJ, Bellet M, Morales S, Ojeda B, Manso L, Mesia C, Garcia-Martínez E, Martinez-Jáñez N, Melé M, Llombart A, Pernas S, Villagrasa P, Blasco C,Baselga J. Breast Cancer Res Treat. 2015 Jun;151(3):597-606.
  8. A phase lb dose escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumours. Bedard P.L., J. Tabernero, F.Janku, Z.A Wainberg, L. Paz-Ares, J. Vansteenkiste, E.Van Cutsem, J. Perez-Garcia, A. Stathis, C.D Britten, N.T. Le, K. Carter, D. Demanse, D. Csonka, M. Peters, A. Zubel, H. Nauwelaerts and C. Sessa. Clin Cancer Res, 2015. 21 (4): p. 730-738.
  9. High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, Chenna A, Winslow J, Serra V, Parra JL, Prudkin L, Jimenez J, Aura C,Harbeck N, Pusztai L, Ellis C, Eidtmann H, Arribas J, Cortes J, de Azambuja E, Piccart M, Baselga J. Clin Cancer Res. 2015 Feb 1;21(3):569-76.
  10. SEOM clinical guidelines in metastatic breast cancer 2015. Gavilá J, Lopez-Tarruella S, Saura C, Muñoz M, Oliveira M, De la Cruz-Merino L, Morales S, Alvarez I, Virizuela JA, Martin M. Clin Transl Oncol. 2015 Dec;17(12):946-55.
  11. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer. Martín M, González-Rivera M, Morales S, de la Haba-Rodriguez J, González-Cortijo L, Manso L, Albanell J, González-Martín A, González S, Arcusa A, de la Cruz-Merino L, Rojo F, Vidal M, Galván P, Aguirre E, Morales C, Ferree S, Pompilio K, Casas M, Caballero R, Goicoechea U, Carrasco E, Michalopoulos S,Hornberger J, Prat A. Curr Med Res Opin. 2015 Jun;31(6):1129-37.
  12. Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile. González-Martín A, Alba E, Ciruelos E, Cortés J, Llombart A, Lluch A, Andrés R, Álvarez I, Aramendía JM, de la Peña FA, Barnadas A, Batista N, Calvo L,Galve E, García-Palomo A, García-Sáenz JÁ, de la Haba J, López R, López-Vivanco G, Martínez-Jáñez N, de Dueñas EM, Plazaola A, Rodríguez-Lescure Á,Ruiz M, Sánchez-Rovira P, Santaballa A, Seguí MÁ, Tusquets I, Zamora P, Martín M. Curr Cancer Drug Targets. 2015 Aug 17. [Epub ahead of print]
  13. Neoadjuvant breast cancer treatment as a sensitive setting for trastuzumab biosimilar development and extrapolation. Jackisch C, Scappaticci FA, Heinzmann D, Bisordi F, Schreitmüller T, Minckwitz Gv, Cortés J. Future Oncol. 2015;11(1):61-71.
  14. Recognizing the place of trials with treatment of physician's choice as the control arm. Twelves C, Jove M, Cortes J. J Clin Oncol. 2015 Apr 10;33(11):1300-1.
  15. Phase III open-lable randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. J Clin Oncol. 2015 Feb 20;33(6):594-601.
  16. Etirinotecan pegol (NKTR-102) versus treatment of physician’s choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomized, open-label, multicenter, phase 3 trial. Perez EA, Awada A, O'Shaughnessy J, Rugo HS, Twelves C, 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, Cortes J. Lancet Oncol. 2015 Nov;16(15):1556-68.
  17. Influencing cancer treatment. Holgado E, J.S Garcia, J.M Perez, A. Wren, J. Cortes and A Gomez-Pinillos. Lancet Oncol. 2015. 16 (16): p. 1591-1593.
  18. Afatinib alone or afatinib plus vinorelbine versus investigator’s choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomized, open-label, multicenter, phase 2 trial. Cortés J, Dieras V, Ro J, Barriere J, Bachelot T, Hurvitz S, Le Rhun E, Espié M, Kim SB, Schneeweiss A, Sohn JH, Nabholtz JM, Kellokumpu-Lehtinen PL, Taguchi J, Piacentini F, Ciruelos E, Bono P, Ould-Kaci M, Roux F, Joensuu H. Lancet Oncol. 2015 Dec;16(16):1700-10.
  19. Gene expression-based classifications of fibroadenomas and phyllodes tumours of the breast. Vidal M, Peg V, Galván P, Tres A, Cortés J, Ramón y Cajal S, Rubio IT, Prat A. Mol Oncol. 2015 Jun;9(6):1081-90.
  20. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. N Engl J Med. 2015 Feb 19;372(8):724-34.
  21. Adjuvant ovarian suppression in premenopausal breast cancer. Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. N Engl J Med. 2015 Jan 29;372(5):436-46.
  22. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Cajal SR, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Nat Commun 2015 Nov 10;6:8839.
  23. Is the Proportion of Patients Diagnosed with Synchronous Stage IV Breast Cancer Who Survive More than Two Years Increasing over Time?. Dawood S, Haaland B, Albaracin C, Gupta S, Cortes J, Sim YY, Dent RA. Oncology. 2015;89(2):79-87.
  24. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Pérez-Garcia J, Masci G, Corsi F, Cortés J, Seoane J, Calin GA, Santarpia L. Oncotarget. 2015 Nov 10;6(35):37269-80.
  25. Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies. Vicario R, Peg V, Morancho B, Zacarias-Fluck M, Zhang J, Martínez-Barriocanal Á, Navarro Jiménez A, Aura C, Burgues O, Lluch A, Cortés J,Nuciforo P, Rubio IT, Marangoni E, Deeds J, Boehm M, Schlegel R, Tabernero J, Mosher R, Arribas J. PLoS One. 2015 Jun 15;10(6):e0129876.
  26. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y,Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen. N,Chandarlapaty S, Scaltriti M, Baselga J. Sci Transl Med. 2015 Apr 15;7(283):283ra51.
  27. Sub-centimeter HER2-Positive Breast Cancer: How Small Is Too Small to Treat? Morris GJ, Dawood S, Cortes J, Ward JH, Vaklavas C, Forero A, Ward S, Toppmeyer D. Semin Oncol. 2015 Aug;42(4):e67-79.
  28. Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. Yardley DA, Brufsky A, Coleman RE, Conte PF, Cortes J, Glück S, Nabholtz JM, O'Shaughnessy J, Beck RM, Ko A, Renschler MF, Barton D, Harbeck N. Trials. 2015 Dec 16;16:575.
  29. Quantification of HER family receptors in breast cancer. Nuciforo P, Radosevic-Robin N, Ng T, Scaltriti M. Breast Cancer Res. 2015 Apr 9;17:53.
  30. Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.
    Nuciforo PG, Aura C, Holmes E, Prudkin L, Jimenez J, Martinez P, Ameels H, de la Peña L, Ellis C, Eidtmann H, Piccart-Gebhart MJ, Scaltriti M, Baselga J. Ann Oncol. 2015 Jul;26(7):1494-500.
  31. PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance. Stern HM, Gardner H, Burzykowski T, Elatre W, O'Brien C, Lackner MR, Pestano GA, Santiago A, Villalobos I, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Nuciforo P, Bee V, Mackey J, Slamon DJ, Press MF. Clin Cancer Res. 2015 May 1;21(9):2065-74.
  32. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer. Majewski IJ, Nuciforo P, Mittempergher L, Bosma AJ, Eidtmann H, Holmes E, Sotiriou C, Fumagalli D, Jimenez J, Aura C, Prudkin L, Díaz-Delgado MC, de la Peña L, Loi S, Ellis C, Schultz N, de Azambuja E, Harbeck N, Piccart-Gebhart M, Bernards R, Baselga J. J Clin Oncol. 2015 Apr 20;33(12):1334-9.
  33. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. Prat A, Fan C, Fernández A, Hoadley KA, Martinello R, Vidal M, Viladot M, Pineda E, Arance A, Muñoz M, Paré L, Cheang MC, Adamo B, Perou CM. BMC Med. 2015 Dec 18;13:303.
  34. Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis. Pavlovic M, Arnal-Estapé A, Rojo F, Bellmunt A, Tarragona M, Guiu M, Planet E, Garcia-Albéniz X, Morales M, Urosevic J, Gawrzak S, Rovira A, Prat A, Nonell L, Lluch A, Jean-Mairet J, Coleman R, Albanell J, Gomis RR. J Natl Cancer Inst. 2015 Sep 15;107(12):djv256.
  35. Whole-transcriptome analysis links trastuzumab sensitivity of breast tumors to both HER2 dependence and immune cell infiltration. Triulzi T, De Cecco L, Sandri M, Prat A, Giussani M, Paolini B, Carcangiu ML, Canevari S, Bottini A, Balsari A, Menard S, Generali D, Campiglio M, Di Cosimo S, Tagliabue E. Oncotarget. 2015 Sep 29;6(29):28173-82.
  36. Clinical implications of the intrinsic molecular subtypes of breast cancer. Prat A, Pineda E, Adamo B, Galván P, Fernández A, Gaba L, Díez M, Viladot M, Arance A, Muñoz M. Breast. 2015 Nov;24 Suppl 2:S26-35.
  37. SOLTI NeoPARP: A phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer. Llombart-Cussac A, Bermejo B, Villanueva C, Delaloge S, Morales S, Balmaña J, Amillano K, Bonnefoi H, Casas A, Manso L, Roché H, Gonzalez-Santiago S, Gavilá J, Sánchez-Rovira P, Di Cosimo S, Harbeck N, Charpentier E, Garcia-Ribas I, Radosevic-Robin N, Aura C, Baselga J. Breast Cancer Res Treat. 2015 Nov;154(2):351-7.
  38. Defining breast cancer intrinsic subtypes by quantitative receptor expression. Cheang MC, Martin M, Nielsen TO, Prat A, Voduc D, Rodriguez-Lescure A, Ruiz A, Chia S, Shepherd L, Ruiz-Borrego M, Calvo L, Alba E, Carrasco E, Caballero R, Tu D, Pritchard KI, Levine MN, Bramwell VH, Parker J, Bernard PS, Ellis MJ, Perou CM, Di Leo A, Carey LA. Oncologist. 2015 May;20(5):474-82.
  39. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J. Sci Transl Med. 2015 Apr 15;7(283):283ra51.
  40. Effect of celular senescence on the growth of HER2-positive breast cancers. Zacarias-Fluck MF, Morancho B, Vicario R, Luque Garcia A, Escorihuela M, Villanueva J, Rubio IT,Arribas J. J Natl Cancer Inst. 2015 May 13;107(5).
  41. Tumor-infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. JAMA Oncol. 2015 Jul;1(4):448-54.
  42. The Hippo effector YAP promotes resistance to RAF and MEK targeted cancer therapies. Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, Pazarentzos E, Asthana S, Neel D, Yan JJ, Lu X, Pham L, Wang MM, Karachaliou N, Cao MG,Manzano JL, Ramirez JL, Torres JM, Buttitta F, Rudin CM, Collisson EA, Algazi A, Robinson E, Osman I, Muñoz-Couselo E, Cortes J, Frederick DT, Cooper ZA, McMahon M, Marchetti A, Rosell R, Flaherty KT, Wargo JA, Bivona TG. Nat Genet. 2015 Mar;47(3):250-6.
  43. Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targetin EGFR. Vizoso M, Ferreira HJ, Lopez-Serra P, Carmona FJ, Martínez-Cardús A, Girotti MR, Villanueva A, Guil S, Moutinho C, Liz J, Portela A, Heyn H,Moran S, Vidal A, Martinez-Iniesta M, Manzano JL, Fernandez-Figueras MT, Elez E, Muñoz-Couselo E, Botella-Estrada R, Berrocal A, Pontén F,Oord Jv, Gallagher WM, Frederick DT, Flaherty KT, McDermott U, Lorigan P, Marais R, Esteller M. Nat Med. 2015 Jul;21(7):741-50.
  44. Recent advances in the treatment of melanoma with BRAF and MEK inhibitors. Muñoz-Couselo E, García JS, Pérez-García JM, Cebrián VO, Castán JC. Ann Transl Med. 2015 Sep;3(15):207.
  45. BRAF mutation analysis in circulating free tumor DNA of melanoma patients treated withBRAF inhibitors. Gonzalez-Cao M, Mayo-de-Las-Casas C, Molina-Vila MA, De Mattos-Arruda L, Muñoz-Couselo E, Manzano JL, Cortes J, Berros JP, Drozdowskyj A, Sanmamed M, Gonzalez A, Alvarez C, Viteri S, Karachaliou N, Martin Algarra S, Bertran-Alamillo J, Jordana-Ariza N, Rosell R. Melanoma Res. 2015 Dec;25(6):486-95.

Projects / Breast Cancer & Melanoma Group

  1. Desvelando las vías moleculares que llevan al desarrollo de la carcinomatosis leptomeníngea.
  2. Predicción precoz de eficacia de la terapia endocrina en cáncer de mama: estudio piloto y validación con 18F-FES.
  3. The big molecular screening feasibility study: Testing the infrastructure and logistics of a molecular screening program.
  4. Prevención de las recaídas mediante ejercicio, dieta y control de peso en pacientes con cáncer de mama.
  5. Molecular screening platform for patients with advanced or metastatic breast cancer.
  6. Sensibilidad a fármacos. Biopsias recogidas/Crecimiento en ratón.
  1. Estudio traslacional de determinación en suero y plasma de BRAFV600 en pacientes con melanoma metastásico BRAFV600.
  2. Cancer mama-BRCA: Estudio de mecanismos genéticos a terapias dirigidas.
  3. Pacientes con Melanoma metastásico de recién diagnóstico. Seguimiento prospectivo de los pacientes BRAF mutados.
  4. Predicción de respuesta a la quimioterapia neoadyuvante con docetaxel-carboplatino en cáncer de mama triple negativo en etapas II/III.
  5. Positive: Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine treatment.

Awards / Breast Cancer & Melanoma Group

  1. We are members of 25 Clinical Trial Steering Committees.
  2. We have received two European grants and one FIS Grant (the Spanish Ministry of Health).
  3. We lead seven large International clinical trials, and are involved in more than 50 active clinical trials.

Early Clinical Drug Development Group / Jordi Rodón

Imagen

Principal Investigator, Early Clinical Drug Development Group, Director & Medical Coordinator, UITM
Jordi Rodón

Director of Clinical Research at VHIO
Josep Tabernero

Associate Investigators
SENIOR CONSULTANTS
Judith Balmaña
Joan Carles
Enriqueta Felip
Ana Oaknin
Cristina Saura
Josep Tabernero

PHASE I RESEARCHERS
Maria Alsina
Analía B. Azaro
Irene Braña
Cristina Cruz
María Elena Élez
Ana Garrido Castro
Patricia Gómez
Julieta Grasselli
Cinta Hierro
Teresa Macarulla

Juan Martín
Alex Martínez
Alejandro Navarro
Maria Ochoa de Olza
Mafalda Oliveira
Jose Manuel Pérez
Tamara Saurí
Cristina Suárez
Claudia Valverde
Helena Verdaguer
Esther Zamora

Summary / Early Clinical Drug Development Group

Our main interest surrounds proof-of-concept and proof-of-mechanism trials with targeted therapies, especially those aimed at cell signaling, cancer stem cells and immuno-oncology. These include firstin-human studies of targeted therapies, rational combinations of targeted therapies, biomarker-driven trials, and trials in molecularly selected populations.

We try to link clinical research at the UITM with the different areas of research carried out at VHIO, following a truly translational model: linking molecular biology and the best tumor models with pharmacology and innovative clinical research. We are therefore dedicated to involving VHIO scientists in our trials (biomarker development, profound understanding of mechanisms of action and resistance) for selected projects. We have collaborated with VHIO’s Molecular Oncology Group, headed by Paolo Nuciforo, as well as the Cancer Genomics Group led by Ana Vivancos, to perform molecular analysis of patients’ tumors in order to select the best possible treatment for our patients with the experimental therapies available in our portfolio of clinical trials - one step closer to realizing the true promise of precision medicine. Importantly, in relation to precision oncology, VHIO is a founding member of the WIN (Worldwide Innovative Networking in personalized cancer medicine) and the Cancer Core Europe Consortia. Both are nongovernmental organizations that bring together international (WIN) and/or European (CCE) cancer centers including VHIO to advance cancer diagnostics and therapeutics, especially in the area of precision medicine.

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.

Strategic Goals / Early Clinical Drug Development Group

  1. Early development of the best-in-class targeted therapies by experienced multidisciplinary teams incorporating physician-researchers from the Research Unit for Molecular Therapy of Cancer (UITM) “la Caixa”, and VHIO scientists.
  2. Accelerate early drug development and translational research through the management and treatment of patients in Phase I trials.
  3. Genomic trials in early drug development; analyzing patients’ tumors for molecular aberrations that may predict the efficacy of targeted agents. Connect preclinical science and clinical research by incorporating novel drugs, new insights and study designs together with molecular diagnostics.
  4. UITM Task Force in early drug development of immunotherapeutics and cell signaling (with special focus on cytokines, immunomodulatory agents and immune checkpoint inhibitors) and translational research in immuno-oncology.
  5. Collaborate with different partners in drug development and translational research (phase I units, academic centers, consortia, pharmaceutical companies).

Highlights 2015 / Early Clinical Drug Development Group

  1. As a leading institute worldwide in drug development (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 bestin-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.
  2. We have performed many clinical trials with novel-novel combinations such as combination of targeted therapies (novel/novel), or, in the area of immunoncology, combining checkpoint inhibitors with either chemo, radiation (abscopal effect), targeted therapies or other immunomodulatory agents (TGFbeta, LAG3, anti VEGFR2, CD40).
  3. We have performed many 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).
  4. We have performed 22 Basket studies. These ‘Baskets’ are a novel type of clinical trial design enabling analysis of the antitumor effect of a given therapy in many small patient populations. We have now designed our Basket of Baskets project to launch in 2017.
  5. Co-development of molecular tests for patient screening (disease-oriented mutation panels for NGS platforms and Nanostring nCounter).

PI Paper Pick / Early Clinical Drug Development Group

Rodon J, Carducci MA, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I Sicart E, Gueorguieva I, Cleverly AL, Pillay NS, Desaiah D, Estrem ST, Paz-Ares L, Holdhoff M, Blakeley J, Lahn MM, Baselga J. First-in.human dose study of the novel transforming growth factor-b receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. Clin Cancer Res. 2015;21(3):553-560.

Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015;33(30):3401-3408.

Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAFV600 Mutations. N Engl J Med. 2015;373(8):726-736.

Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015;372(18):1689-1699.

Horizons 2016 / Early Clinical Drug Development Group

  1. Expand our number of clinical trials adding new targeted therapies against novel promising targeted therapies and best-in-class therapies.
  2. Increase our portfolio of molecular tests, adding new probes to our collection of MiSeq and Nanostring panels, as well as incorporate a new generation of platforms for molecular analysis such as mutational analysis of tumors samples in circulating tumor DNA (BEAMing).
  3. To develop expertise in the emerging field of cell signaling between tumor cells and the immune system and early drug development of therapies that modulate that signaling.
  4. To continue our participation in the field of precision cancer medicine, with the aim of developing a second trial looking at personalized combinations of drugs through patient-derived primary cultures in order to predict drug sensitivity. In this regard, we will raise funds for the Basket of Baskets project, endorsed by Cancer Core Europe.
  5. To train 3-4 oncologists in early drug development and translational research.

Publications / Early Clinical Drug Development Group

  1. Hierro C, Rodon J, Tabernero J. Fibroblast Growth Factor (FGF) Receptor/FGF Inhibitors: Novel Targets and Strategies for Optimization of Response of Solid Tumors. Semin Oncol. 2015 Dec;42(6):801-19.
  2. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8.
  3. Arqués O, Chicote I, Puig I, Tenbaum SP, Argilés G, Dienstmann R, Fernández N, Caratù G, Matito J, Silberschmidt D, Rodon J, Landolfi S, Prat A, Espín E, Charco R, Nuciforo P, Vivancos A, Shao W, Tabernero J, Palmer HG. Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer. Clin Cancer Res. 2016 Feb 1;22(3):644-56.
  4. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med. 2015 Apr15;7(283):283ra51.
  5. Elkabets M, Pazarentzos E, Juric D, Sheng Q, Pelossof RA, Brook S, Benzaken AO, Rodon J, Morse N, Yan JJ, Liu M, Das R, Chen Y, Tam A, Wang H, Liang J, Gurski JM, Kerr DA, Rosell R, Teixidó C, Huang A, Ghossein RA, Rosen N, Bivona TG, Scaltriti M, Baselga J. AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas. Cancer Cell. 2015 Apr 13;27(4):533-46.
  6. Spreafico A, Delord JP, De Mattos-Arruda L, Berge Y, Rodon J, Cottura E, Bedard PL, Akimov M, Lu H, Pain S, Kaag A, Siu LL, Cortes J. A first-in-human phase I, dose-escalation, multicentre study of HSP990 administered orally in adult patients with advanced solid malignancies. Br J Cancer. 2015 Feb 17;112(4):650-9.
  7. Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2015 Jan;149(1):151-61.
  8. de Gramont A, Watson S, Ellis LM, Rodón J, Tabernero J, de Gramont A, Hamilton SR. Pragmatic issues in biomarker evaluation for targeted therapies in cancer. Nat Rev Clin Oncol. 2015 Apr;12(4):197-212. doi: 10.1038/nrclinonc.2014.202.
  9. Élez E, Kocáková I, Höhler T, Martens UM, Bokemeyer C, Van Cutsem E, Melichar B, Smakal M, Csőszi T, Topuzov E, Orlova R, Tjulandin S, Rivera F, Straub J, Bruns R, Quaratino S, Tabernero J. Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015 Jan;26(1):132-40.
  10. Dienstmann R, Rodon J, Tabernero J. Optimal design of trials to demonstrate the utility of genomically-guided therapy: Putting Precision Cancer Medicine to the test. Mol Oncol. 2015 May;9(5):940-50. doi: 10.1016/j.molonc.2014.06.014.
  11. Zeron-Medina J, Ochoa de Olza M, Braña I, Rodon J. The Personalization of Therapy: Molecular Profiling Technologies and Their Application. Semin Oncol. 2015 Dec;42(6):775-87.
  12. González-Cao M, Rodón J, Karachaliou N, Sánchez J, Santarpia M, Viteri S, Pilotto S, Teixidó C, Riso A, Rosell R. Other targeted drugs in melanoma. Ann Transl Med. 2015 Oct;3(18):266.
  13. Dienstmann R, Lassen U, Cebon J, Desai J, Brown MP, Evers S, Su F, Zhang W, Boisserie F, Lestini B, Schostack K, Meresse V, Tabernero J. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2015 Aug 27.
  14. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-36.
  15. García-García C, Rivas MA, Ibrahim YH, Calvo MT, Gris-Oliver A, Rodríguez O, Grueso J, Antón P, Guzmán M, Aura C, Nuciforo P, Jessen K, Argilés G, Dienstmann R, Bertotti A, Trusolino L, Matito J, Vivancos A, Chicote I, Palmer HG, Tabernero J, Scaltriti M, Baselga J, Serra V. MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer. Clin Cancer Res. 2015 Dec 15;21(24):5499-510.
  16. Sepulveda-Sanchez J, Ramos A, Hilario A, DE Velasco G, Castellano D, Garcia DE LA Torre M, Rodon J, Lahn MF. Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate. Oncol Lett. 2015 Jun;9(6):2442-2448.
  17. Juric D, Dienstmann R, Cervantes A, Hidalgo M, Messersmith W, Blumenschein GR Jr, Tabernero J, Roda D, Calles A, Jimeno A, Wang X, Bohórquez SS, Leddy C, Littman C, Kapp AV, Shames DS, Penuel E, Amler LC, Pirzkall A, Baselga J. Safety and Pharmacokinetics/Pharmacodynamics of the First-in-Class Dual Action HER3/EGFR Antibody MEHD7945A in Locally Advanced or Metastatic Epithelial Tumors. Clin Cancer Res. 2015 Jun 1;21(11):2462-70.
  18. Macarulla T, Cervantes A, Tabernero J, Roselló S, Van Cutsem E, Tejpar S, Prenen H, Martinelli E, Troiani T, Laffranchi B, Jego V, von Richter O, Ciardiello F. Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer. Br J Cancer. 2015 Jun9;112(12):1874-81.
  19. Lazar V, Rubin E, Depil S, Pawitan Y, Martini JF, Gomez-Navarro J, Yver A, Kan Z, Dry JR, Kehren J, Validire P, Rodon J, Vielh P, Ducreux M, Galbraith S, Lehnert M, Onn A, Berger R, Pierotti MA, Porgador A, Pramesh CS, Ye DW, Carvalho AL, Batist G, Le Chevalier T, Morice P, Besse B, Vassal G, Mortlock A, Hansson J, Berindan-Neagoe I, Dann R, Haspel J, Irimie A, Laderman S, Nechushtan H, Al Omari AS, Haywood T, Bresson C, Soo KC, Osman I, Mata H, Lee JJ, Jhaveri K, Meurice G, Palmer G, Lacroix L, Koscielny S, Eterovic KA, Blay JY, Buller R, Eggermont A, Schilsky RL, Mendelsohn J, Soria JC, Rothenberg M, Scoazec JY, Hong WK, Kurzrock R. A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer. Oncotarget. 2015 Jun 10;6(16):14139-52.
  20. Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99.
  21. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D, Matthews SE, Cantarini M, Barrett JC, Jänne PA, Oxnard GR. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015 Jun;21(6):560-2.
  22. Rodon J, Soria JC, Berger R, Batist G, Tsimberidou A, Bresson C, Lee JJ, Rubin E, Onn A, Schilsky RL, Miller WH, Eggermont AM, Mendelsohn J, Lazar V, Kurzrock R. Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial. Ann Oncol. 2015 Aug;26(8):1791-8.
  23. Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol. 2015 Jun 1;33(16):1787-96.
  24. Azaro A, Rodon J, Calles A, Braña I, Hidalgo M, Lopez-Casas PP, Munoz M, Westwood P, Miller J, Moser BA, Ohnmacht U, Bumgardner W, Benhadji KA, Calvo E. A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer. Invest New Drugs. 2015 Jun;33(3):710-9.
  25. Brown JR, Davids MS, Rodon J, Abrisqueta P, Kasar SN, Lager J, Jiang J, Egile C, Awan FT. Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. Clin Cancer Res. 2015 Jul 15;21(14):3160-9.
  26. Mau-Sørensen M, Dittrich C, Dienstmann R, Lassen U, Büchler W, Martinius H, Tabernero J. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Cancer Chemother Pharmacol. 2015 May;75(5):1065-73.
  27. Agarwal R, Liebe S, Turski ML, Vidwans SJ, Janku F, Garrido-Laguna I, Munoz J, Schwab R, Rodon J, Kurzrock R, Subbiah V; Pan-Cancer Working Group. Targeted therapy for genetic cancer syndromes: Von Hippel-Lindau disease, Cowden syndrome,and Proteus syndrome. Discov Med. 2015 Feb;19(103):109-16. Review.
  28. Agarwal R, Liebe S, Turski ML, Vidwans SJ, Janku F, Garrido-Laguna I, Munoz J, Schwab R, Rodon J, Kurzrock R, Subbiah V; Pan-Cancer Working Group. Targeted therapy for genetic cancer syndromes: Fanconi anemia, medullary thyroid cancer,tuberous sclerosis, and RASopathies. Discov Med. 2015 Feb;19(103):101-8.
  29. Shapiro GI, Bell-McGuinn KM, Molina JR, Bendell J, Spicer J, Kwak EL, Pandya SS, Millham R, Borzillo G, Pierce KJ, Han L, Houk BE, Gallo JD, Alsina M, Braña I, Tabernero J. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
  30. Di Stefano AL, Fucci A, Frattini V, Labussiere M, Mokhtari K, Zoppoli P, Marie Y, Bruno A, Boisselier B, Giry M, Savatovsky J, Touat M, Belaid H, Kamoun A, Idbaih A, Houillier C, Luo FR, Soria JC, Tabernero J, Eoli M, Paterra R, Yip S, Petrecca K, Chan JA, Finocchiaro G, Lasorella A, Sanson M, Iavarone A. Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type Glioma. Clin Cancer Res. 2015 Jul 15;21(14):3307-17.
  31. Rodón J, Carducci M, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I, Sicart E, Gueorguieva I, Cleverly A, Pillay NS, Desaiah D, Estrem ST, Paz-Ares L, Holdhoff M, Blakeley J, Lahn MM, Baselga J. Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer. Invest New Drugs. 2015 Apr;33(2):357-70.
  32. Bedard PL, Tabernero J, Janku F, Wainberg ZA, Paz-Ares L, Vansteenkiste J, Van Cutsem E, Pérez-García J, Stathis A, Britten CD, Le N, Carter K, Demanse D, Csonka D, Peters M, Zubel A, Nauwelaerts H, Sessa C. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res. 2015 Feb 15;21(4):730-8.
  33. Shou Y, Robinson DM, Amakye DD, Rose KL, Cho YJ, Ligon KL, Sharp T, Haider AS, Bandaru R, Ando Y, Geoerger B, Doz F, Ashley DM, Hargrave DR, Casanova M, Tawbi HA, Rodon J, Thomas AL, Mita AC, MacDonald TJ, Kieran MW. A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma. Clin Cancer Res. 2015 Feb 1;21(3):585-93.
  34. Rodon J, Carducci MA, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I, Sicart E, Gueorguieva I, Cleverly AL, Pillay NS, Desaiah D, Estrem ST, Paz-Ares L, Holdhoff M, Blakeley J, Lahn MM, Baselga J. First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. Clin Cancer Res. 2015Feb 1;21(3):553-60.
  35. Papadopoulos KP, Egile C, Ruiz-Soto R, Jiang J, Shi W, Bentzien F, Rasco D, Abrisqueta P, Vose JM, Tabernero J. Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, XL765), an orally administered phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or refractory lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1763-70.

Projects / Early Clinical Drug Development Group

  1. 360 resistance: Matched therapies, resistance mechanisms and tumor heterogeneity.
  2. Cellular Plasticity and Cancer.
  3. Deciperhing PI3K biology in health and disease.
  4. Potenciación de la Citotoxicidad dependiente de Anticuerpo mediada por linfocitos NK para Inmunoterápia del cáncer.
  1. 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).
  2. Estudio de las alteraciones de FGFR como posible mecanismo de resistencia en pacientes que reciben tratamiento con pan-inhibidores de FGFR.
  3. Basket of Baskets, from Cancer Core Europe.
  4. MedBioinformatics.

Gastrointestinal & Endocrine Tumors Group / Josep Tabernero

Imagen

Principal Investigator
Josep Tabernero

Medical Oncologists and Clinical Fellows
Maria Alsina
Guillem Argilés
Jaume Capdevila
María Elena Élez
Julieta Grasselli
Teresa Macarulla
Ignacio Matos
Tamara Saurí
Helena Verdaguer

Clinical Nurse Specialist
Ariadna García

Summary / Gastrointestinal & Endocrine Tumors Group

In 2015, we have led and participated in numerous cooperative and singular research projects related to Gastrointestinal Malignancies. In addition to our key participation in existing international consortia of excellence including Cancer Core Europe and the FP-7 supported COLTHERES, EurocanPlatform, and MerCuRIC Consortia, I am delighted to announce that 2015 celebrated the launch of the MoTricolor Consortium. Spurred by EU’s Horizon 2020 program, and led by VHIO, this pan-European project will design and lead Molecularly guided Trials with specific treatment strategies in patients with advanced newly molecular defined subtypes of Colorectal cancer, and for the first time, stratify patients based on their gene expression profiles according to recently established predictive signatures. We will collectively aim to identify sensitivity of individual patients to the proposed experimental therapies towards ultimately developing more precise anti-cancer therapies.

Reflected by publications in the most prestigious scientific titles in 2015, our group has also led and collaborated in studies with important clinical implications, just some of which include:

  • Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. Mayer RJ et al. 2015. N Engl J Med. 372: 1909-1919. This international Phase III study evidenced that TAS-102, an oral antitumor agent combining a duo of drugs (trifluridine & tipiracil hydrochloride), improved overall survival by two months for patients with treatmentresistant metastatic CRC.
  • Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. Hyman DM. et al. 2015. N Engl J Med. 373: 726-736. This phase II basket trial co-designed and led by our group, enrolled patients who had different types of cancer with the BRAFV600 mutation, and showed the efficacy of vemurafenib as therapy against multiple tumor types that share this mutation.
  • Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Tabernero J et al. 2015. Lancet Oncol.16: 499-508. The large RAISE multicenter international trial reported significant improvement in the global survival of patients with metastatic CRC who were treated with a combination of ramucirumab and chemotherapy as second-line treatment.
  • Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wildtype metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Elez E et al. 2015. Ann Oncol. 26:132-40. This early phase trial assessed the tolerability and efficacy of abituzumab in combination with cetuximab and irinotecan in patients with metastatic CRC. Predefined exploratory biomarker analyses identified subgroups of patients for whom abituzumab may have benefit.

We continue to develop next generation blood-based diagnostics to monitor disease, its respective molecular specificities, and response to novel targeted therapies. Findings from the first large clinical trial to compare liquid versus conventional tissue biopsy data, the CORRECT phase III study, showed that BEAMing technology produced more data on tumor mutation throughout the course of the disease (Tabernero J. et al. 2015. Lancet Oncol. 16: 937-948).

Lastly, our group has participated in several pre-clinical and clinical studies on predicted responsive patient subsets using genetically annotated tumor surgical specimens (‘Xenopatients’) in mice, further expanding our collaboration with VHIO’s Stem Cells & Cancer Group.

Strategic Goals / Gastrointestinal & Endocrine Tumors Group

  1. Discovery of novel biomarkers in gastrointestinal tumorigenesis.
  2. Validation of new prognostic biomarkers.
  3. Development of relevant preclinical models in vitro and in vivo with emphasis on the identification of predictive markers.
  4. Molecular characterization of major diseases, with particular focus on colorectal cancer, in different targetable subtypes.
  5. Early clinical research with innovative targets.
  6. Clinical research in late stage with more translational endpoints, focusing on the identification of prognostic/predictive biomarkers.
  7. Design of/increased participation in novel Basket trials.
  8. Participation in multidisciplinary/multinational consortia and collaborative research programs of excellence.
  9. Validation of repurposed drugs or candidate drugs, in partnership with pharma companies or academic groups.
  10. Expansion of our collaboration with other VHIO teams (Proteomics, Tumor Biomarkers, Cancer Genomics, Translational Genomics, and Stem Cells & Cancer Groups).

Highlights 2015 / Gastrointestinal & Endocrine Tumors Group

  1. Early drug development and Phase I clinical trials in solid tumors with particular emphasis on developing molecular targeted therapies.
  2. 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.
  3. Design of investigator-initiated clinical trials as well as participation in numerous trials developed in the context of national and international cooperative groups.
  4. Co-designed and led by our group and colleagues at the Memorial Sloan Kettering Cancer Center (MSKCC, New York), a phase II novel basket trial evidenced the efficacy of vemurafenib as therapy against multiple tumor types that share the BRAFV600 mutation, Hyman DM et al. 2015. N Engl J Med. 373:726-736.
  5. Studies evidencing improved treatment efficacy against metastatic colorectal cancer led to important publications incl. Mayer RJ et al. 2015 N Engl J Med. 372: 1909-1919 and, Tabernero J et al. 2015. Lancet Oncol. 16: 937-948.
  6. Led by VHIO, the Horizon 2020-funded MoTricolor Consortium will design and conduct multi-center early phase trials to identify anti-tumor activity of novel therapies against CRCm.

PI Paper Pick / Gastrointestinal & Endocrine Tumors Group

Mayer RJ; Van Cutsem E; Falcone A; Yoshino T; Garcia-Carbonero R; Mizunuma N; Yamazaki K; Shimada Y; Tabernero J; Komatsu Y; Sobrero A; Boucher E; Peeters M; Tran B; Lenz HJ; Zaniboni A; Hochster H; Cleary JM;Prenen H; Benedetti F; Mizuguchi H; Makris L; Ito M; Ohtsu A. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. N Engl J Med. 2015;372(20):1909-1919.

Hyman DM; Puzanov I; Subbiah V; Faris JE; Chau I; Blay JY; Wolf J; Raje NS; Diamond EL; Hollebecque A; Gervais R; Elez E; Italiano A; Hofheinz RD; Hidalgo M; Chan E; Schuler M; Lasserre SF; Makrutzki M; Sirzen F; Veronese ML; Tabernero J; Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015;373(8):726-736.

Tabernero J; Yoshino T; Cohn AL; Obermannova R; Bodoky G; Garcia-Carbonero R; Ciuleanu TE; Portnoy DC; Van Cutsem E; Grothey A; Prausová J; Garcia-Alfonso P; Yamazaki K; Clingan PR; Lonardi S; Kim TW; Simms L; Chang SC; Nasroulah F. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508.

Elez E; Kocáková I; Höhler T; Martens UM; Bokemeyer C; Van Cutsem E; Melichar B; Smakal M; Csoszi T; Topuzov E; Orlova R; Tjulandin S; Rivera F; Straub J; Bruns R; Quaratino S; Tabernero J. Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015;26(1):132-140.

Horizons 2016 / Gastrointestinal & Endocrine Tumors Group

  1. Lead the design of/increased participation in novel Basket trials.
  2. 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.
  3. Validation of repurposed drugs or candidate drugs, in partnership with pharma companies or academic groups.
  4. Expansion of our collaboration with other VHIO teams (Proteomics, Tumor Biomarkers, Cancer Genomics, Translational Genomics, and Stem Cells & Cancer Groups).

Publications / Gastrointestinal & Endocrine Tumors Group

  1. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. Mayer RJ; Van Cutsem E; Falcone A; Yoshino T; Garcia-Carbonero R; Mizunuma N; Yamazaki K; Shimada Y; Tabernero J; Komatsu Y; Sobrero A; Boucher E; Peeters M; Tran B; Lenz HJ; Zaniboni A; Hochster H; Cleary JM; Prenen H; Benedetti F; Mizuguchi H; Makris L; Ito M; Ohtsu A. 2015. N. Engl. J. Med. 372: 1909-1919.
  2. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. Hyman DM; Puzanov I; Subbiah V; Faris JE; Chau I; Blay JY; Wolf J; Raje NS; Diamond EL; Hollebecque A; Gervais R; Elez E; Italiano A; Hofheinz RD; Hidalgo M; Chan E; Schuler M; Lasserre SF; Makrutzki M; Sirzen F; Veronese ML; Tabernero J; Baselga J. 2015. N. Engl. J. Med. 373: 726-736.
  3. Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Vizoso M; Ferreira HJ; Lopez-Serra P; Carmona FJ; Martínez-Cardús A; Girotti MR; Villanueva A; Guil S; Moutinho C; Liz J; Portela A; Heyn H; Moran S; Vidal A; Martinez-Iniesta M; Manzano JL; Fernandez-Figueras MT; Elez E; Muñoz E; Botella-Estrada R; Berrocal A; Pontén F; Oord JV; Gallagher WM; Frederick DT; Flaherty KT; McDermott U; Lorigan P; Marais R; Esteller M. 2015. Nat. Med. 21: 741-0.
  4. The consensus molecular subtypes of colorectal cancer. Guinney J; Dienstmann R; Wang X; de Reyniès A; Schlicker A; Soneson C; Marisa L; Roepman P; Nyamundanda G; Angelino P; Bot BM; Morris JS; Simon IM; Gerster S; Fessler E; De Sousa E Melo F; Missiaglia E; Ramay H; Barras D; Homicsko K; Maru D; Manyam GC; Broom B; Boige V; Perez-Villamil B; Laderas T; Salazar R; Gray JW; Hanahan D; Tabernero J; Bernards R; Friend SH; Laurent-Puig P; Medema JP; Sadanandam A; Wessels L; Delorenzi M; Kopetz S; Vermeulen L; Tejpar S. 2015. Nat. Med. 21: 1350-1356.
  5. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Tabernero J; Lenz HJ; Siena S; Sobrero A; Falcone A; Ychou M; Humblet Y; Bouché O; Mineur L; Barone C; Adenis A; Yoshino T; Goldberg RM; Sargent DJ; Wagner A; Laurent D; Teufel M; Jeffers M; Grothey A; Van Cutsem E. 2015. Lancet Oncol. 16: 937-948.
  6. Correction to Lancet Oncol 2015; 16: 499-508. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Tabernero J; Takayuki Y; Cohn AL. 2015. Lancet Oncol.
  7. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Tabernero J; Yoshino T; Cohn AL; Obermannova R; Bodoky G; Garcia-Carbonero R; Ciuleanu TE; Portnoy DC; Van Cutsem E; Grothey A; Prausová J; Garcia-Alfonso P; Yamazaki K; Clingan PR; Lonardi S; Kim TW; Simms L; Chang SC; Nasroulah F. 2015. Lancet Oncol. 16: 499-508.
  8. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Brastianos PK; Carter SL; Santagata S; Cahill DP; Taylor-Weiner A; Jones RT; Van Allen EM; Lawrence MS; Horowitz PM; Cibulskis K; Ligon KL; Tabernero J; Seoane J; Martinez-Saez E; Curry WT; Dunn IF; Paek SH; Park SH; McKenna A; Chevalier A; Rosenberg M; Barker FG; Gill CM; Van Hummelen P; Thorner AR; Johnson BE; Hoang MP; Choueiri TK; Signoretti S; Sougnez C; Rabin MS; Lin NU; Winer EP; Stemmer-Rachamimov A; Meyerson M; Garraway L; Gabriel S; Lander ES; Beroukhim R; Batchelor TT; Baselga J; Louis DN; Getz G; Hahn WC. 2015. Cancer Discov. 5: 1164-1177.
  9. Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Dienstmann R; Patnaik A; Garcia-Carbonero R; Cervantes A; Benavent M; Roselló S; Tops BB; van der Post RS; Argilés G; Skartved NJ; Hansen UH; Hald R; Pedersen MW; Kragh M; Horak ID; Braun S; Van Cutsem E; Tolcher AW; Tabernero J. 2015. Cancer Discov. 5: 598-609.
  10. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. André T; de Gramont A; Vernerey D; Chibaudel B; Bonnetain F; Tijeras-Raballand A; Scriva A; Hickish T; Tabernero J; Van Laethem JL; Banzi M; Maartense E; Shmueli E; Carlsson GU; Scheithauer W; Papamichael D; Möehler M; Landolfi S; Demetter P; Colote S; Tournigand C; Louvet C; Duval A; Fléjou JF; de Gramont A. 2015. J. Clin. Oncol. 33: 4176-0.
  11. Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. Schmoll HJ; Tabernero J; Maroun J; de Braud F; Price T; Van Cutsem E; Hill M; Hoersch S; Rittweger K; Haller DG. 2015. J. Clin. Oncol. 33: 3733-0.
  12. Personalizing Colon Cancer Adjuvant Therapy: Selecting Optimal Treatments for Individual Patients. Dienstmann R; Salazar R; Tabernero J. 2015. J. Clin. Oncol. 33: 1787-0.
  13. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. Tabernero J; Bahleda R; Dienstmann R; Infante JR; Mita A; Italiano A; Calvo E; Moreno V; Adamo B; Gazzah A; Zhong B; Platero SJ; Smit JW; Stuyckens K; Chatterjee-Kishore M; Rodon J; Peddareddigari V; Luo FR; Soria JC. 2015. J. Clin. Oncol. 33: 3401-0.
  14. Progression-Free Survival: Helpful Biomarker or Clinically Meaningless End Point? Venook AP; Tabernero J. 2015. J. Clin. Oncol. 33: 4-15.
  15. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study. Geva R; Vecchione L; Kalogeras KT; Jensen BV; Lenz HJ; Yoshino T; Paez D; Montagut C; Souglakos J; Cappuzzo F; Cervantes A; Frattini M; Fountzilas G; Johansen JS; Høgdall EV; Zhang W; Yang D; Yamazaki K; Nishina T; Papamichael D; Vincenzi B; Macarulla T; Loupakis F; De Schutter J; Spindler KL; Pfeiffer P; Ciardiello F; Piessevaux H; Tejpar S. 2015. Gut. 64: 921-928.
  16. Pragmatic issues in biomarker evaluation for targeted therapies in cancer. de Gramont A; Watson S; Ellis LM; Rodón J; Tabernero J; de Gramont A; Hamilton SR. 2015. Nat. Rev. Clin. Oncol. 12: 197-212.
  17. A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS Wild-Type, Metastatic Colorectal Cancer. 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; Frödin JE; Ayers M; Nebozhyn M; Peckitt C; Loboda A; Mauro DJ; Watkins DJ. 2015. JNCI-J. Natl. Cancer Inst.
  18. nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer: Long-Term Survival From a Phase III Trial. Goldstein D; El-Maraghi RH; Hammel P; Heinemann V; Kunzmann V; Sastre J; Scheithauer W; Siena S; Tabernero J; Teixeira L; Tortora G; Van Laethem JL; Young R; Penenberg DN; Lu B; Romano A; Von Hoff DD. 2015. JNCI-J. Natl. Cancer Inst.
  19. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. De Mattos-Arruda L; Mayor R; Ng CK; Weigelt B; Martínez-Ricarte F; Torrejon D; Oliveira M; Arias A; Raventos C; Tang J; Guerini-Rocco E; Martínez-Sáez E; Lois S; Marín O; de la Cruz X; Piscuoglio S; Towers R; Vivancos A; Peg V; Cajal SR; Carles J; Rodon J; González-Cao M; Tabernero J; Felip E; Sahuquillo J; Berger MF; Cortes J; Reis-Filho JS; Seoane J. 2015. Nat. Commun. 6: 8839-0.
  20. A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies. Gupta S; Argiles G; Munster PN; Hollebecque A; Dajani O; Cheng J; Wang R; Swift A; Tosolini A; Piha-Paul SA. 2015. Clin. Cancer Res. 21: 5235-5244.
  21. A Phase Ib Dose-Escalation Study of the Oral Pan-PI3K Inhibitor Buparlisib (BKM120) in Combination with the Oral MEK1/2 Inhibitor Trametinib (GSK1120212) in Patients with Selected Advanced Solid Tumors. Bedard PL; Tabernero J; Janku F; Wainberg ZA; Paz-Ares L; Vansteenkiste J; Van Cutsem E; Perez-Gercia J; Stathis A; Britten CD; Le NT; Carter K; Demanse D; Csonka D; Peters M; Zubel A; Nauwelaerts H; Sessa C. 2015. Clin. Cancer Res. 21: 730-738.
  22. Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type Glioma. Di Stefano AL; Fucci A; Frattini V; Labussiere M; Mokhtari K; Zoppoli P; Marie Y; Bruno A; Boisselier B; Giry M; Savatovsky J; Touat M; Belaid H; Kamoun A; Idbaih A; Houiller C; Luo FR; Soria JC; Tabernero J; Eoli M; Paterra R; Yip S; Petrecca K; Chan JA; Finocchiaro G; Lasorella A; Sanson M; Iavarone A. 2015. Clin. Cancer Res. 21: 3307-3317.
  23. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Shapiro GI; Bell-McGuinn KM; Molina JR; Bendell JC; Spicer J; Kwak EL; Pandya SS; Millham R; Borzillo G; Pierce KJ; Han L; Houk BE; Gallo JD; Alsina M; Brana I; Tabernero J. 2015. Clin. Cancer Res. 21: 1888-1895.
  24. MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer. Celina GG; Rivas MA; Ibrahim YH; Calvo MT; Gris-Oliver A; Rodriguez O; Grueso J; Anton P; Guzman M; Aura C; Nuciforo P; Jessen K; Argiles G; Dienstmann R; Bertotti A; Trusolino L; Matito J; Vivancos A; Chicote I; Palmer HG; Tabernero J; Scaltriti M; Baselga J; Serra V. 2015. Clin. Cancer Res. 21: 5499-5510.
  25. Safety and Pharmacokinetics/Pharmacodynamics of the First-in-Class Dual Action HER3/EGFR Antibody MEHD7945A in Locally Advanced or Metastatic Epithelial Tumors. Juric D; Dienstmann R; Cervantes A; Hidalgo M; Messersmith W; Blumenschein GR; Tabernero J; Roda D; Calles A; Jimeno A; Wang X; Bohórquez SS; Leddy C; Littman C; Kapp AV; Shames DS; Penuel E; Amler LC; Pirzkall A; Baselga J. 2015. Clin. Cancer Res. 21: 2462-2470.
  26. SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial. Hidalgo M; Plaza C; Musteanu M; Illei P; Brachmann CB; Heise C; Pierce DW; Lopez-Casas PP; Menendez C; Tabernero J; Romano A; Wei X; Lopez-Rios F; Von Hoff DD. 2015. Clin. Cancer Res. 21: 4811-4818.
  27. Optimising translational oncology in clinical practice: Strategies to accelerate progress in drug development. Stahel R; Bogaerts J; Ciardiello F; de Ruysscher D; Dubsky P; Ducreux M; Finn S; Laurent-Puig P; Peters S; Piccart M; Smit E; Sotiriou C; Tejpar S; Van Cutsem E; Tabernero J. 2015. Cancer Treat. Rev. 41: 129-135.
  28. Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors. Jiménez-Fonseca P; Carmona-Bayonas A; Martín-Pérez E; Crespo G; Serrano R; Llanos M; Villabona C; García-Carbonero R; Aller J; Capdevila J; Grande E; Spanish Neuroendocrine Tumor Group (GETNE). 2015. Cancer Metastasis Rev.34: 381-400.
  29. Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development. Garcia-Carbonero R; Garcia-Figueiras R; Carmona-Bayonas A; Sevilla I; Teule A; Quindos M; Grande E; Capdevila J; Aller J; Arbizu J; Jimenez-Fonseca P; Spanish Cooperative Group of Neuroendocrine Tumors (GETNE). 2015. Cancer Metastasis Rev. 34: 823-842.
  30. A phase I/II, open-label, randomised study of nintedanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in first-line metastatic colorectal cancer patients. Van Cutsem E; Prenen H; D'Haens G; Bennouna J; Carrato A; Ducreux M; Bouché O; Sobrero A; Latini L; Staines H; Oum'Hamed Z; Dressler H; Studeny M; Capdevila J. 2015. Ann. Oncol. 26: 2085-2091.
  31. Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Elez E; Kocáková I; Höhler T; Martens UM; Bokemeyer C; Van Cutsem E; Melichar B; Smakal M; Csoszi T; Topuzov E; Orlova R; Tjulandin S; Rivera F; Straub J; Bruns R; Quaratino S; Tabernero J. 2015. Ann. Oncol. 26: 132-140.
  32. Cyclin E amplification/overexpression is associated with poor prognosis in gastric cancer. Alsina M; Landolfi S; Aura C; Caci K; Jimenez J; Prudkin L; Castro S; Moreno D; Navalpotro B; Tabernero J; Scaltriti M. 2015. Ann. Oncol. 26: 438-439.
  33. Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study. Van Cutsem E; Boni C; Tabernero J; Massuti B; Middleton G; Dane F; Reichardt P; Pimentel FL; Cohn A; Follana P; Clemens M; Zaniboni A; Moiseyenko V; Harrison M; Richards DA; Prenen H; Pernot S; Ecstein-Fraisse E; Hitier S; Rougier P. 2015. Ann. Oncol. 26: 149-156.
  34. Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)(aEuro). Grande E; Capdevila J; Castellano D; Teule A; Duran I; Fuster J; Sevilla I; Escudero P; Sastre J; García-Donas J; Casanovas O; Earl J; Ortega L; Apellaniz-Ruiz M; Rodriguez-Antona C; Alonso T; Díez JJ; Carrato A; García-Carbonero R. 2015. Ann. Oncol. 26: 1987-1993.
  35. Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial. Sclafani F; Chau I; Cunningham D; Peckitt C; Lampis A; Hahne JC; Braconi C; Tabernero J; Glimelius B; Cervantes A; Begum R; Gonzalez De Castro D; Hulkki Wilson S; Eltahir Z; Wotherspoon A; Tait D; Brown G; Oates J; Valeri N. 2015. Ann. Oncol. 26: 1936-1941.
  36. Proven efficacy, equitable access, and adjusted pricing of anti-cancer therapies: no `sweetheart' solution. Tabernero J. 2015. Ann. Oncol. 26: 1529-1531.
  37. Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer. Sotelo MJ; Sastre J; Maestro ML; Veganzones S; Viéitez JM; Alonso V; Grávalos C; Escudero P; Vera R; Aranda E; García-Alfonso P; Gallego-Plazas J; Lopez C; Pericay C; Arrivi A; Vicente P; Ballesteros P; Elez E; López-Ladrón A; Díaz-Rubio E. 2015. Ann. Oncol. 26: 535-541.
  38. Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Douillard JY; Siena S; Peeters M; Koukakis R; Terwey JH; Tabernero J. 2015. Eur. J. Cancer. 51: 1231-1242.
  39. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial. Argilés G; Saunders MP; Rivera F; Sobrero A; Benson A; Guillén Ponce C; Cascinu S; Van Cutsem E; Macpherson IR; Strumberg D; Köhne CH; Zalcberg J; Wagner A; Luigi Garosi V; Grunert J; Tabernero J; Ciardiello F. 2015. Eur. J. Cancer. 51: 942-949.
  40. Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours. Piha-Paul SA; Munster PN; Hollebecque A; Argilés G; Dajani O; Cheng JD; Wang R; Swift A; Tosolini A; Gupta S. 2015. Eur. J. Cancer. 51: 1865-1873.
  41. Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy. Ruff P; Ferry DR; Lakom? R; Prausová J; Van Hazel GA; Hoff PM; Cunningham D; Arnold D; Schmoll HJ; Moiseyenko VM; McKendrick JJ; Ten Tije AJ; Vishwanath RL; Bhargava P; Chevalier S; Macarulla T; Van Cutsem E. 2015. Eur. J. Cancer. 51: 18-26.
  42. Optimal design of trials to demonstrate the utility of genomically-guided therapy: Putting Precision Cancer Medicine to the test. Dienstmann R; Rodon J; Tabernero J. 2015. Mol. Oncol. 9: 940-950.
  43. Genomic Classifier ColoPrint Predicts Recurrence in Stage II Colorectal Cancer Patients More Accurately Than Clinical Factors. Kopetz S; Tabernero J; Rosenberg R; Jiang ZQ; Moreno V; Bachleitner-Hofmann T; Lanza G; Stork-Sloots L; Maru D; Simon I; Capellà G; Salazar R. 2015. Oncologist. 20: 127-133.
  44. Prognostic Factors of Survival in a Randomized Phase III Trial (MPACT) of Weekly nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer. Tabernero J; Chiorean EG; Infante JR; Hingorani SR; Ganju V; Weekes C; Scheithauer W; Ramanathan RK; Goldstein D; Penenberg DN; Romano A; Ferrara S; Von Hoff DD. 2015. Oncologist. 20: 143-150.
  45. Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer. Macarulla T; Cervantes A; Tabernero J; Roselló S; Van Cutsem E; Tejpar S; Prenen H; Martinelli E; Troiani T; Laffranchi B; Jego V; von Richter O; Ciardiello F. 2015. Br. J. Cancer. 112: 1874-1881.
  46. Short-and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial. Sclafani F; Peckitt C; Cunningham D; Tait D; Giralt J; Glimelius B; Keränen SR; Bateman A; Hickish T; Tabernero J; Thomas J; Brown G; Oates J; Chau I. 2015. Int. J. Radiat. Oncol. Biol. Phys.. 93: 303-312.
  47. GEP-NETs UPDATE Biotherapy for neuroendocrine tumours. Alonso-Gordoa T; Capdevila J; Grande E. 2015. Eur. J. Endocrinol.
  48. Fibroblast Growth Factor (FGF) Receptor/FGF Inhibitors: Novel Targets and Strategies for Optimization of Response of Solid Tumors. Hierro C; Rodon J; Tabernero J. 2015. Semin. Oncol. 42: 801-819.
  49. Methodological aspects of the molecular and histological study of prostate cancer: Focus on PTEN. Ugalde-Olano A; Egia A; Fernández-Ruiz S; Loizaga-Iriarte A; Zuñiga-Garcia P; Garcia S; Royo F; Lacasa-Viscasillas I; Castro E; Zabala-Letona A; Martín-Martín N; Arruabarrena-Aristorena A; Torrano-Moya V; Valcarcel-Jimenez L; Sanchez-Mosquera P; Caro-Maldonado A; Gonzalez-Tampan J; Cachi-Fuentes G; Bilbao E; Montero R; Fernández S; Arrieta E; Zorroza K; Castillo-Martín M; Serra V; Salazar E; Macias-Camara N; Tabernero J; Baselga J; Cordon-Cardo C; Aransay AM; Villar AD; Iovanna JL; Falcón-Pérez JM; Unda M; Bilbao R; Carracedo A. 2015. Methods. 77-78: 25-30.
  50. A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features. Salazar R; Capdevila J; Laquente B; Manzano JL; Pericay C; Villacampa MM; López C; Losa F; Safont MJ; Gómez A; Alonso V; Escudero P; Gallego J; Sastre J; Grávalos C; Biondo S; Palacios A; Aranda E. 2015. BMC Cancer. 15: 60-0.
  51. Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis. Capdevila J; Sevilla I; Alonso V; Antón Aparicio L; Jiménez Fonseca P; Grande E; Reina JJ; Manzano JL; Alonso Lájara JD; Barriuso J; Castellano D; Medina J; López C; Segura Á; Carrera S; Crespo G; Fuster J; Munarriz J; García Alfonso P. 2015. BMC Cancer. 15: 495-0.
  52. Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies. Vicario R; Peg V; Morancho B; Zacarias-Fluck M; Zhang J; Martínez-Barriocanal Á; Navarro Jiménez A; Aura C; Burgues O; Lluch A; Cortés J; Nuciforo P; Rubio IT; Marangoni E; Deeds J; Boehm M; Schlegel R; Tabernero J; Mosher R; Arribas J. 2015. PLoS One.
  53. Intrinsic cancer subtypes-next steps into personalized medicine. Santos C; Sanz-Pamplona R; Nadal E; Grasselli J; Pernas S; Dienstmann R; Moreno V; Tabernero J; Salazar R. 2015. Cell. Oncol. 38: 3-16.
  54. Impact of prior chemotherapy use on the efficacy of everolimus in patients with advanced pancreatic neuroendocrine tumors: a subgroup analysis of the phase III RaDIaNT-3 trial. Lombard-Bohas C; Yao JC; Hobday T; Van Cutsem E; Wolin EM; Panneerselvam A; Stergiopoulos S; Shah M; Capdevila J; Pommier R. 2015. Pancreas. 44: 181-189.
  55. Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, XL765), an orally administered phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or refractory lymphoma. Papadopoulos KP; Egile C; Ruiz-Soto R; Jiang J; Shi W; Bentzien F; Rasco D; Abrisqueta P; Vose JM; Tabernero J. 2015. Leuk. Lymphoma. 56: 1763-1770.
  56. Pharmacokinetic and pharmacodynamic evaluation of aflibercept for the treatment of colorectal cancer. Sanz-Garcia E; Saurí T; Tabernero J; Macarulla T. 2015. Expert Opin. Drug Metab. Toxicol. 11: 995-1004.
  57. First-Line Treatment of Metastatic Colorectal Cancer: Interpreting FIRE-3, PEAK, and CALGB/SWOG 80405. Elez E; Argilés G; Tabernero J. 2015. Curr. Treat. Options Oncol. 16: 52-0.
  58. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Mau-Sørensen M; Dittrich C; Dienstmann R; Lassen U; Büchler W; Martinius H; Tabernero J. 2015. Cancer Chemother. Pharmacol. 75: 1065-1073.
  59. Expert consensus for the management of advanced or metastatic pancreatic neuroendocrine and carcinoid tumors. Castellano D; Grande E; Valle J; Capdevila J; Reidy-Lagunes D; O'Connor JM; Raymond E. 2015. Cancer Chemother. Pharmacol. 75: 1099-1114.
  60. Phase II trial of miniDOX (reduced dose docetaxel-oxaliplatin-capecitabine) in "suboptimal" patients with advanced gastric cancer (AGC). TTD 08-02. Rivera F; Massutí B; Salcedo M; Sastre J; Martínez Galán J; Valladares-Ayerbes M; Serrano R; García de Paredes ML; Manzano JL; Galán M; Alsina M; Yuste Izquierdo AL; López C; Díaz-Rubio E; Conde V; Reboredo M; Cano MT; Pachón V; Aranda E. 2015. Cancer Chemother. Pharmacol. 75: 319-324.
  61. Genomic Testing in Colorectal Cancer: How Much Is Enough?. Dienstmann R; Salazar R; Tabernero J. 2015. Oncology-NY. 29: 186-188.
  62. Biliary tract cancers: SEOM clinical guidelines. Benavides M; Antón A; Gallego J; Gómez MA; Jiménez-Gordo A; La Casta A; Laquente B; Macarulla T; Rodríguez-Mowbray JR; Maurel J. 2015. Clin. Transl. Oncol. 17: 982-987.
  63. Paraneoplastic limbic encephalitis in a male with squamous cell carcinoma of the lung. Sauri T; Izquierdo À; Ramió-Torrentà L; Sanchez-Montañez À; Bosch-Barrera J; Porta R. 2015. J CLIN NEUROL. 11: 87-91.
  64. Cost-utility analysis of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine in metastatic pancreatic cancer in Spain: results of the PANCOSTABRAX study. Carrato A; García P; López R; Macarulla T; Rivera F; Sastre J; Gostkorzewicz J; Benedit P; Pérez-Alcántara F. 2015. Expert Rev Pharmacoecon Outcomes Res. 15: 579-589.
  65. Overcoming Resistance to Anti-EGFR Therapy in Colorectal Cancer. Dienstmann R; Salazar R; Tabernero J. 2015. Am Soc Clin Oncol Educ Book.
  66. Consensus on the management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI). Galofré JC; Santamaría Sandi J; Capdevila J; Navarro González E; Zafón Llopis C; Ramón Y Cajal Asensio T; Gómez Sáez JM; Jiménez-Fonseca P; Riesco Eizaguirre G; Grande E. 2015. Endocrinol Nutr.

Projects / Gastrointestinal & Endocrine Tumors Group

  1. 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).
  2. Rational Therapy for Breast Cancer (RATHER).
  3. A European Platform for Translational Cancer Research (Eurocan Platform).
  4. MErCuRIC: A Phase Ib/II Study of MEK1/2 Inhibitor PD-0325901 with cMET Inhibitor PF-02341066 in KRASMT and KRASWT (with Aberrant c-MET) Colorectal Cancer Patients.
  5. Screening Platform of the EORTC for Clinical Trials in Advanced Colorectal Cancer “SPECTAcolor”.
  6. Identificación de biomarcadores predictivos de respuesta y Resistencia a tratamientos biológicos.
  1. Estudio de las mutaciones de las vías MAP quinasas en pacientes con cáncer colorrectal metastásico (mCRC)-inhibidores B-REF.
  2. Estudio de la implementación clínica de los subtipos moleculares consensuados en cáncer colorrectal.
  3. Molecularly guided trials with specific treatment strategies in patients with advanced newly molecular defined subtypes of colorectal cancer (MoTriColor).
  4. Identificación de biomarcadores predictivos de respuesta y Resistencia a tratamientos biológicos.
  5. Evolution of resistant clones to novel target-directed drugs in colorectal tumors. A genetic and epigenetic study of intratumoral heterogeneity dynamics (IntraColor).
  6. Synergy in the Identification and Application of Biomarkers for Improved Cancer Therapy at Massachusetts General Hospital Cancer Center and Vall d´Hebron Institute of Oncology.

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

Imagen

Principal Investigator
Joan Carles

Medical Oncologists and Clinical Fellows
Rafael Morales
Jordi Rodón
César Serrano
Cristina Suárez
Claudia Valverde

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

Our group is interested in both clinical and translational research with broad experience and grounded expertise in the treatment of different neoplasms. We design and develop clinical trials for genitourinary malignancies at different stages of disease in collaboration with urologists and radiation therapists.

Over recent years, many developments have been reported in GU tumors; particularly in prostate, bladder and kidney cancer. Immunotherapy is proving increasingly important in the treatment of bladder and kidney cancer. We have been able to participate in different clinical trials using checkpoint inhibitors. Close collaboration with all specialists involved in the treatment of these tumors is consequently essential. We are also focused on the continued development of our translational research platform for urologic cancer, as well as conducting clinical trials in early, adjuvant as well as metastatic disease.

Our group collaborates with other research centers of excellence including the Cleveland Clinic (USA), University of California San Francisco (USA), Gustave Roussy Hospital (France), and the Biomedical Research Institute of Bellvitge (IDIBELL), here in Barcelona (Spain). We have developed the avatar program for kidney cancer tumors in collaboration with IDIBELL and have now implanted more than 20 samples. Another key area is the development of several multidisciplinary clinical studies and phase I trials in CNS tumors, in close collaboration with professionals in neurosurgery and radiation therapy. We are also dedicated to expanding our translational research platform for glioblastoma in collaboration with VHIO’s Gene Expression & Cancer Group led by Joan Seoane. We have consolidated a collaborative study with different centers across Europe to develop a vaccine for patients with glioblastoma and we are now initiating the phase I program. This project is supported by the European Commission’s 7th Framework Programme of Research and Development.

Our group works closely with the Spanish Sarcoma Group (GEIS) to conduct clinical trials at different stages of disease with emphasis on a histology-tailored design. We 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 work in partnership with J. Fletcher’s lab at Brigham and Women’s Hospital (USA).

Cesar Serrano joined our group as VHIO researcher in 2014 having spent the previous three years at Brigham and Women’s Hospital. He was awarded a Grant from the SARC (Sarcoma Alliance for Research through Collaboration) to develop new therapies against GIST tumors. We are currently developing novel strategies in GIST therapy in close collaboration with other referral centers throughout Europe and pharmaceutical companies.

The serum bank has expanded to include the majority of our tumor types (CNS tumors, GIST; renal cell carcinoma and CRPC) and will continue to recruit samples from our patients. Importantly in terms of education and exchange, in 2015 we welcomed five fellows from in and out Spain to visit our group for short stays of three months.

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

  1. Design and develop clinical trials for the malignancies covered by our group. We provide patients with the most novel and optimal treatments for their respective diesease, including immunotherapeutics, targeted therapies, and new chemotherapeutics.
  2. Conduct clinical trials at different stages of disease with emphasis on a histology-tailored design and a multidisciplinary approach.
  3. Develop new approaches such as liquid biopsy to better tailor treatments against CRPC, GIST, and kidney cancer.
  4. Expand our translational research platform for glioblastoma in collaboration with VHIO’s Gene Expression & Cancer Group.
  5. Create a translational platform for kidney cancer and sarcomas and basic research in partnership with the Biomedical Research Institute of Bellvitge (IDIBELL).
  6. Set up a translational platform for GIST and expand research in collaboration with the Spanish Sarcoma Group (GEIS) and other European referral Centers.

PI Paper Pick / Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group

Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152-60.

Smith MR, Rathkopf DE, Mulders PF, Carles J, Van Poppel H, Li J, Kheoh T, Griffin TW, Molina A, Ryan CJ. Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naïve Patients with Metastatic Castration Resistant Prostate Cancer. J Urol. 2015;194(5):1277-1284.

Climent MÁ, León-Mateos L, González Del Alba A, Pérez-Valderrama B, Méndez-Vidal MJ, Mellado B, Arranz JÁ, Sánchez-Hernández A, Cassinello J, Olmos D, Carles J. Updated recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with metastatic castration-resistant prostate cancer. Crit Rev Oncol Hematol. 2015;96(2):308-318.

De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015;6:8839.

Horizons 2016 / Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group

In 2016 we aim to consolidate clinical research in the Sarcoma field and progress in the treatment of GIST. We will also seek to accelerate tailored treatments in GU malignancies and CNS tumors with the goal of developing our translational research in both tumor types:

  1. In prostate cancer in parallel with the development of innovative clinical trials with special focus on the androgen receptor and vaccines. We will consolidate a serum bank for all patients with CRPC and try to develop new tools (Beaming) to select more precise treatments for our patients.
  2. In renal cell we will develop a close relationship with the Cleveland Clinic and will start working developing new biomarkers in collaboration with other hospitals in Spain. Also for renal cell carcinoma we are implementing the Avatar program and aim to develop the same strategy in all others high risk subpopulations GU tumors.
  3. Develop new treatments in CNS according to the mouse model developed by VHIO´s Gene Expression and Cancer Group, mainly related to PI3K and TGF beta inhibitors. Also correlate those data with circulating DNA from patients with CNS tumors.

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 allow new studies on innovative drugs and therapeutic leads to improve the pharmacological treatments for cancer and reduce their toxicity.

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

  1. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Lancet Oncol. 2015 Feb;16(2):152-60.
  2. KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation. Serrano C, Wang Y, Mariño-Enríquez A, Lee JC, Ravegnini G, Morgan JA, Bertagnolli MM, Beadling C, Demetri GD, Corless CL, Heinrich MC, Fletcher JA. J Clin Oncol. 2015 Aug 1;33(22):e93-6.
  3. New advances in genitourinary cancer: evidence gathered in 2014. Suárez C, Puente J, Gallardo E, Méndez-Vidal MJ, Climent MA, León L, Olmos D, García del Muro X, González-Billalabeitia E, Grande E, Bellmunt J, Mellado B, Maroto P, González del Alba A. Cancer Metastasis Rev. 2015 Sep;34(3):443-64.
  4. Role of surgery in patients with recurrent, metastatic, or unresectable locally advanced gastrointestinal stromal tumors sensitive to imatinib: a retrospective analysis of the Spanish Group for Research on Sarcoma (GEIS). Rubió-Casadevall J, Martínez-Trufero J, Garcia-Albeniz X, Calabuig S, Lopez-Pousa A, Del Muro JG, Fra J, Redondo A, Lainez N, Poveda A, Valverde C, De Juan A, Sevilla I, Casado A, Andrés R, Cruz J, Martín-Broto J, Maurel J; Spanish Group for Research on Sarcoma (GEIS). Ann Surg Oncol. 2015 Sep; 22(9): 2948-57.
  5. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, Yu EY, Powles T, Moshier EL, Ladoire S, Hussain SA, Agarwal N, Vaishampayan UN, Recine F, Berthold D, Necchi A, Theodore C, Milowsky MI, Bellmunt J, Rosenberg JE; Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators. Cancer. 2015 Aug 1;121(15):2586-93.
  6. Identification of somatic gene mutations in penile squamous cell carcinoma. Ferrándiz-Pulido C, Hernández-Losa J, Masferrer E, Vivancos A, Somoza R, Marés R, Valverde C, Salvador C, Placer J, Morote J, Pujol RM, Ramon y Cajal S, de Torres I, Toll A, García-Patos V. Genes Chromosomes Cancer. 2015 Oct;54(10):629-37.
  7. Second-Line Chemotherapy for Metastatic Urothelial Carcinoma: Importance of Lymph Node-Only Metastasis as a Prognostic Factor and Construction of a Prognostic Model. Salah S, Lee JL, Rozzi A, Kitamura H, Matsumoto K, Srinivas S, Morales-Barrera R, Carles J, Al-Wardat R, Al-Rabi K, Maakoseh M. Clin Genitourin Cancer. 2015 Oct 24. (Epub ahead of print).
  8. Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naïve Patients with Metastatic Castration Resistant Prostate Cancer. Smith MR, Rathkopf DE, Mulders PF, Carles J, Van Poppel H, Li J, Kheoh T, Griffin TW, Molina A, Ryan CJ. J Urol. 2015 Nov;194(5):1277-84.
  9. Updated recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with metastatic castration-resistant prostate cancer. Climent MÁ, León-Mateos L, González Del Alba A, Pérez-Valderrama B, Méndez-Vidal MJ, Mellado B, Arranz JÁ, Sánchez-Hernández A, Cassinello J, Olmos D, Carles J. Crit Rev Oncol Hematol. 2015 Nov;96(2):308-18.
  10. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Nat Commun. 2015 Nov 10;6:8839.
  11. Prognostic implications of epilepsy in glioblastomas. Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martínez-Ricarte F, Rodon J, Auger C, Salas-Puig J, Santamarina E, martinez-Saez E. Clin Neurol Neurosurg. 2015 Dec; 139-166-71.
  12. Expert Recommendations for First-Line Management of Metastatic Renal Cell Carcinoma in Special Subpopulations. Puente J, García Del Muro X, Pinto Á, Láinez N, Esteban E, Arranz JÁ, Gallardo E, Méndez MJ, Maroto P, Grande E, Suárez C. Target Oncol. 2015 Dec 26. (Epub ahead of print).
  13. Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study. Pérez-Valderrama B, Arranz Arija JA, Rodríguez Sánchez A, Pinto Marín A, Borrega García P, Castellano Gaunas DE, Rubio Romero G, Maximiano Alonso C, villa Guzmán JP, Puertas Álvarez JL, Chirivella González I, Méndez Vidal MJ, Juan Fita MJ, León-Mateos L, Lázaro Quintela M, García Domínguez R, Jurado García JM, Vélez de mendizábal E, Lambea Sorrosal JJ, García Carbonero I, González del Alba A, Suárez Rodríguez C, Jiménez Gallego P, Meana García JA, García Marrero RD, Gajate Borau P, Santander Lobera C, Molins Palau C, López Brea M, Fernández Parra EM, Reig Torras O, Basterretxea Badiola L, Vázquez Estévez S, González Larriba JL. Ann Oncol. 2015 Dec 9. (Epub ahead of print).

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

  1. Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC)
    Reference: RISC
    Principal Investigator: Rafael Morales
  2. 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
  3. 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
  4. 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
  5. Sequence in men with metastasic castration-resistant prostate cancer: a European, retrospective, observational study
    Reference: CATS
    Principal Investigator: Rafael Morales
  6. Estudio de cDNA en cáncer de próstata resistente a la castración. (SEROTECA)
    Reference: Seroteca
    Principal Investigator: Joan Carles
  7. 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
  8. 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
  9. 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)
  10. 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
  11. CTC-SOGUG: Determinación de CTCs en el seguimiento de enfermos tratados con Radium 223.
    Principal Investigator: Joan Carles
  12. 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
  13. Estudio de factores de susceptibilidad genética en Cáncer de Testículo (Colaboración CNIO multicéntrico nacional)
    Principal Investigator: Claudia Valverde
  1. Estudio de mecanismos de resistencia a antiangiogénicos (ICO)
    Principal Investigator: Cristina Suárez
  2. Análisis comparativo de patrones micro RNAs de riñones embrionarios y tumores renales
    Principal Investigator: Cristina Suárez
  3. Modelo de avatar PDX para predicción de la sensibilidad a fármacos
    Principal Investigator: Cristina Suárez
  4. SPAZO 2: Pazopanib en la vida real
    Principal Investigator: Cristina Suárez
  5. Perfil genético mutacional en pacientes con cáncer renal metastásico tratados con inhibidores de mTOR
    Principal Investigator: Cristina Suárez
  6. Senescencia en Sarcomas y GIST
    Principal Investigator: Claudia Valverde
  7. Colaboración en distintas bases de datos: Germinales, Sarcomas de partes blandas, Osteosarcomas y GIST (GEIS), Carcinoma Suprarrenal (GETHI)
    Principal Investigator: Claudia Valverde
  8. 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
  9. Papel de HER-3 en TMVNP esporádico y asociado a NF-1
    Principal Investigator: Claudia Valverde
  10. 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
  11. 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
  12. 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
  13. Prognostic relevance of miRNA let-7e in localized intestinal GIST. A Spanish Group for Research on Sarcoma (GEIS) study
    Principal Investigator: Claudia Valverde
  14. Estudio observacional de largos respondedores GIST
    Reference: GEIS45
    Principal Investigator: Claudia Valverde
  15. Caracterización molecular del CP en función de la expresión TMPRSS2-ERG: Implicaciones terapéuticas
    Principal Investigator: Cristina Suárez
  16. Análisis retrospectivo de la influencia de: AAS, Antilipolipemiantes e hipoglicemiantes en la evolución del CPRC
    Principal Investigator: Joan Carles

Gynecological Malignancies Group / Ana Oaknin

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Principal Investigator
Ana Oaknin

Medical Oncologist and Clinical Fellow
Lorena Fariñas

Summary / Gynecological Malignancies Group

Our group mainly focuses on clinical research in gynecological malignancies. We are majorly involved in the development of new therapies in the treatment of gynecologic tumors. Notably, our clinical research work has led to approval of new standard of care in both resistant relapsed ovarian cancer ( e.g. AURELIA Trial) and in metastatic cervical cancer (e.g. GOG240 trial).

Our clinical research is largely developed through our close collaboration with other international renowned research groups of excellence. We are active members of some of the most relevant societies in gynecological oncology including the Gynecologic Cancer Inter Group (GCIG) serving 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). In addition, our group’s PI, Ana Oaknin serves on the Executive Board as Vice President for the Grupo Español de Investigación en Cáncer de Ovario (Spanish Gynecological Group - GEICO). Such involvement allows us to initiate the development of new drugs and novel treatment approaches from the very outset, which in turn, provides our patients with greater opportunity to potentially benefit from these research efforts.

It is thanks to our strong and expanding clinical research endeavors aimed at advancing treatment and care for gynecological tumors, coupled with our established reputation for excellence, that we serve as a Reference Site for the majority of regional hospitals and sites at national level. This position of leadership has consequently led to a steady increase in the number of patients treated with new therapies in our clinical trials and, most importantly, provided new hope for these patients.

We are currently leading clinical studies with novel PARP inhibitors for both patients with ovarian cancer associated to the BRCA mutation as well as a welldefined group of patients with high grade ovarian carcinoma. These new drugs have the potential to change the course of history in the treatment of ovarian cancer since they act at specific molecular points in DNA repair pathways. Our group also has a keen interest in immunotherapy and angiogenesis.

In parallel with our clinical research, we play a central and key role as members of multidisciplinary committees and teams in Gynecological Cancer Tumors at the Vall d’Hebron University Hospital (HUVH). Our involvement, in close connectivity and collaboration with other professionals and specialties (including surgeons, radiotherapists, radiologists and pathologists), contributes to establishing new treatment protocols and clinical guidelines to further advance clinical practice within our Hospital.

We are continuously invited to participate at international conferences of excellence through the delivery of presentations, invited lectures, and the sharing and debating of key findings with colleagues and peers across the globe.

Strategic Goals / Gynecological Malignancies Group

  1. We are focused on clinical research in gynecological cancer in order to improve outcomes for our patients. Our goal is to play an active part in the development of new drugs from the early beginning, from Phase I clinical trials, and later, through to Phase II and III trials. We are determined that as many of our patients as possible may stand to benefit from the best available treatments, at the earliest stages.
  2. In order to advance research at clinical level, we are dedicated to fostering and developing close collaboration with VHIO colleagues at preclinical level in order to translate insights into the molecular basis of gynecological cancers into benefits for patients, as swiftly as possible.

Highlights 2015 / Gynecological Malignancies Group

  1. As a result of our outstanding clinical research, our group has (co) authored pivotal studies in both cervical and ovarian cancer which have subsequently changed the standard of care of these malignancies.
  2. As lead investigator for GOG in Spain, we have been able to participate in some of the most interesting and practice changing studies in gynecological tumors.
  3. Our participation in the GCIG Cervical Cancer Committee to develop novel anti-cancer therapies.
  4. Ana Oaknin’s Vice Presidency of the GEICO group. This role has allowed our group to help lead clinical research into gynecological malignancies throughout Spain.

Horizons 2016 / Gynecological Malignancies Group

  1. Clinical research will naturally remain a key priority throughout 2016.
  2. We will seek to yet further collaborate with other researchers in order to develop diagnostic, prognostic or predictive tools that facilitate early diagnosis tests in ovarian and endometrial cancer as well as improve current approaches to treatment.

PI Paper Pick / Gynecological Malignancies Group

McMeekin S, Dizon D, Barter J, Scambia G, Manzyuk L, Lisyanskaya A, Oaknin A, Ringuette S, Mukhopadhyay P, Rosenberg J, Vergote I. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015;138(1):18-23.

Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long HJ 3rd, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ1, Leitao MM, Method M, Michael H, Tewari KS3. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol. 2015;16(3):301-311.

Amit M Oza, David Cibula, Ana Oaknin, Christopher Poole, Ron H J Mathijssen, Gabe S Sonke, Nicoletta Colombo, Jiří Špaček, Peter Vuylsteke, Holger Hirte, Sven Mahner, Marie Plante, Barbara Schmalfeldt, Helen Mackay, Jacqui Rowbottom, Elizabeth S Lowe, Brian Dougherty, J Carl Barrett, Michael Friedlander. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015;16(1):87-97.

Oaknin A, Rubio MJ, Redondo A, De Juan A, Cueva Bañuelos JF, Gil-Martin M, Ortega E, Garcia-Arias A,Gonzalez-Martin A, Bover I. SEOM guidelines for cervical cancer. Clin Transl Oncol. 2015;17(12):1036-1042. Epub 2015 Dec 9.

Publications / Gynecological Malignancies Group

  1. Penson RT; Huang HQ; Wenzel LB; Monk BJ; Stockman S; Long HJ; Ramondetta LM; Landrum LM; Oaknin A; Reid TJ; Leitao MM; Method M; Michael H; Tewari KS. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). 2015. Lancet Oncol. 16: 301-311.
  2. Oza AM; Cibula D; Benzaquen AO; Poole C; Mathijssen RH; Sonke GS; Colombo N; Špacek J; Vuylsteke P; Hirte H; Mahner S; Plante M; Schmalfeldt B; Mackay H; Rowbottom J; Lowe ES; Dougherty B; Barrett JC; Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. 2015. Lancet Oncol. 16: 87-97.
  3. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Oza AM; Cook AD; Pfisterer J; Embleton A; Ledermann JA; Pujade-Lauraine E; Kristensen G; Carey MS; Beale P; Cervantes A; Park-Simon TW; Rustin G; Joly F; Mirza MR; Plante M; Quinn M; Poveda A; Jayson GC; Stark D; Swart AM; Farrelly L; Kaplan R; Parmar MK; Perren TJ; ICON7 trial investigators. 2015. Lancet Oncol. 16: 928-936.
  4. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. McMeekin S; Dizon D; Barter J; Scambia G; Manzyuk L; Lisyanskaya A; Oaknin A; Ringuette S; Mukhopadhyay P; Rosenberg J; Vergote I. 2015. Gynecol. Oncol.138: 18-23.
  5. Progression-free survival by local investigator versus independent central review: Comparative analysis of the AGO-OVAR16 Trial. Floquet A; Vergote I; Colombo N; Fiane B; Monk BJ; Reinthaller A; Calvert P; Herzog TJ; Meier W; Kim JW; Del Campo JM; Friedlander M; Pisano C; Isonishi S; Crescenzo RJ; Barrett C; Wang K; Mitrica I; du Bois A. 2015. Gynecol. Oncol. 136: 37-42.
  6. b>SEOM guidelines for cervical cancer.Oaknin A; Rubio MJ; Redondo A; De Juan A; Cueva Bañuelos JF; Gil-Martin M; Ortega E; Garcia-Arias A; Gonzalez-Martin A; Bover I. 2015. Clin. Transl. Oncol. 17: 1036-1042.
  7. The European Network for Gynaecological Oncological Trial Groups Charta for Privileged Partnership. Marth C; du Bois A; Schauer C; du Bois A; Casado A; Vergote I; Del Campo JM; Goudopoulou A; Pujade-Lauraine E; Bruchim I; Colombo N; Pignata S; Ledermann J; Chekerov R; Raza Mirza M; Westermann A; Glasspool R; Taskiran C; Fehr M; Cibula D. 2015. Int. J. Gynecol. Cancer. 25: 1094-1095.

High Risk & Cancer Prevention Group / Judith Balmaña

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Principal Investigator
Judith Balmaña

Staff Scientists
Estela Carrasco
Cristina Cruz
Irene Esteban

Clinical Nurse Specialist
Neus Gadea

Summary / High Risk & Cancer Prevention Group

We are committed to developing new targeted therapies for patients with hereditary breast cancer. During 2015, 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. Consolidation of our collaboration with other VHIO groups led by Violeta Serra, Ana Vivancos, and Orland Díez, has resulted in a large collection of BRCA-associated patientderived xenografts implanted in athymic mice. These murine models are being used to identify mechanisms of resistance to targeted therapies, identify novel biomarkers, and test new combinatorial treatments at progression.

In the field of genetic epidemiology we are mainly focused on identifying new genetic susceptibilities to hereditary breast cancer. We are collaborating with VHIO’s Oncogenetics Group headed by Orland Díez on next generation sequencing studies with a panel of 98 cancer susceptibility genes in breast cancer families with no mutation in BRCA1/BRCA2. Analysis of the first 120 families has provided 9 genetic results with clinical utility. We are committed to performing cosegregation analysis in these families and investigating the cancer spectrum and phenotype of these lesser-known non-BRCA genes. In hereditary colorectal cancer we are participating in a study to identify mutations in POLD1 and POLE in families with polyposis, or young-onset colorectal cancer with microsatellite stability; and we are participating in a national registry led by the EPICOLON group to describe the characteristics of extracolonic tumors in Lynch syndrome mutation carriers.

Our group continues to actively participate in the international multi-center IMPACT study to analyze the efficacy of early detection of prostate cancer in patients with a mutation in the BRCA1/2 genes, as well as an additional study aimed at the characterization of prostate cancer in BRCA and MMR-deficient mutation carriers.

Strategic Goals / High Risk & Cancer Prevention Group

  1. Clinical development of specific therapeutic strategies for tumors associated with hereditary genetic alterations.
  2. Identification of mechanisms of resistance to targeted therapies in BRCA-associated breast cancer.
  3. Testing new combinations of therapies for BRCA-associated PDX’s that have progressed to PARP inhibitors.
  4. Identification of new genes involved in hereditary breast cancer through the application of nextgeneration sequencing (NGS).
  5. Psychological impact of hereditary cancer multiplex gene testing in the Spanish population.

Highlights 2015 / High Risk & Cancer Prevention Group

  1. Active participation in international Phase II and Phase III clinical trials with targeted therapies for BRCA-associated tumors.
  2. Establishing a large collection of BRCA-associated patient-derived xenografts implanted in athymic mice.
  3. Preliminary analysis -- prevalence and clinical utility, of multiplex panel testing in hereditary breast cancer patients without mutations in BRCA1 or BRCA2.

PI Paper Pick / High Risk & Cancer Prevention Group

Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33(3):244-250.

Balmaña J, Domchek SM. BRIP1 as an ovarian cancer susceptibility gene: ready for the clinic? J Natl Cancer Inst. 2015;107(11).

Kastrinos F, Ojha RP, Leenen C, Alvero C, Mercado RC, Balmaña J, Valenzuela I, Balaguer F, Green R, Lindor NM, Thibodeau SN, Newcomb P, Win AK, Jenkins M, Buchanan DD, Bertario L, Sala P, Hampel H, Syngal S, Steyerberg EW; Lynch Syndrome prediction model validation study group. Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer. J Natl Cancer Inst. 2016;108(2). Epub 2015 Nov 18.

Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016;140(2):199-203. Epub 2015 Dec 23.

Horizons 2016 / High Risk & Cancer Prevention Group

  1. 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.
  2. Identify genetic mechanisms of resistance to targeted therapies in BRCA-associated breast cancer and functional biomarkers of sensitivity/resistance.
  3. Test novel combinations of targeted therapies in a patient-derived xenograft model from patients with a germline BRCA mutation.
  4. Establish strategies for the clinical application of next-generation sequencing (a multigene panel), for diagnosis of breast cancer susceptibility.
  5. Investigate the prevalence, cancer spectrum, phenotype, and clinical utility of non-BRCA breast cancer susceptibility genes

Publications / High Risk & Cancer Prevention Group

  1. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50.
  2. Ramón Y Cajal T, Chirivella I, Miranda J, Teule A, Izquierdo Á, Balmaña J, Sánchez-Heras AB, Llort G, Fisas D, Lope V, Hernández-Agudo E, Juan-Fita MJ, Tena I, Robles L, Guillén-Ponce C, Pérez-Segura P, Luque-Molina MS, Hernando-Polo S, Salinas M, Brunet J, Salas-Trejo MD, Barnadas A, Pollán M. Mammographic density and breast cancer in women from high risk families. Breast Cancer Res. 2015 Jul 11;17:93.
  3. Aguirre E, Graña B, Boudet M, Balmaña J. Screening for Lynch syndrome among patients with newly diagnosed endometrial cancer: a comprehensive review. Tumori. 2015 Jul 15.
  4. Balmaña J, Domchek SM. BRIP1 as an ovarian cancer susceptibility gene: ready for the clinic? J Natl Cancer Inst. 2015 Aug 27;107(11).
  5. Llombart-Cussac A, Bermejo B, Villanueva C, Delaloge S, Morales S, Balmaña J, Amillano K, Bonnefoi H, Casas A, Manso L, Roché H, Gonzalez-Santiago S, Gavilá J, Sánchez-Rovira P, Di Cosimo S, Harbeck N, Charpentier E, Garcia-Ribas I, Radosevic-Robin N, Aura C, Baselga J. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer. Breast Cancer Res Treat. 2015 Nov;154(2):351-7.
  6. Kastrinos F, Ojha RP, Leenen C, Alvero C, Mercado RC, Balmaña J, Valenzuela I, Balaguer F, Green R, Lindor NM, Thibodeau SN, Newcomb P, Win AK, Jenkins M, Buchanan DD, Bertario L, Sala P, Hampel H, Syngal S, Steyerberg EW; Lynch Syndrome prediction model validation study group. Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer. J Natl Cancer Inst. 2015 Nov 18;108(2). pii: djv308.
  7. Llort G, Chirivella I, Morales R, Serrano R, Sanchez AB, Teulé A, Lastra E, Brunet J, Balmaña J, Graña B; SEOM Hereditary Cancer Working Group. SEOM clinical guidelines in Hereditary Breast and ovarian cancer. Clin Transl Oncol. 2015 Dec;17(12):956-61.
  8. PARP inhibitors in ovarian cancer. Cibula D, Balmaña J. Br J Cancer. 2015 Dec 15;113 Suppl 1:S1-2.
  9. Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203.

Projects / High Risk & Cancer Prevention Group

  1. BRCA-Associated Breast Cancer: Genetic Mechanisms of Resistance to Targeted Therapies and Analysis of New Treatments in a Patient-Derived Xenograft Model
    Reference: FIS- PI12/02606
    Principal Investigator: Judith Balmaña
  2. Identificación de variantes del ARNm de BRCA que codifican para proteínas con capacidad funcional, como potencial nuevo mecanismo de resistencia a los inhibidores de PARP en cáncer de mama con mutación germinal de BRCA
    SEOM - BUCKLER 0,0.
    Principal Investigator: Cristina Cruz
  1. Identification of BRCA-RNAm Variants that Codify for Functional Proteins as a New Mechanism of Resistance to PARP Inhibitors in GBRCA-Associated Breast Cancer
    Principal Investigator: Cristina Cruz
  2. Identification of Molecular Predictors Associated to Bad Prognosis in GBRCA-Associated Breast Cancer and Analysis of New Therapeutic Strategies
    AECC Grantz
    Principal Investigator: Cristina Cruz

Oncogenetics Group / Orland Díez

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Principal Investigator
Orland Díez

Senior Scientist
Sara Gutiérrez

Post-Doctoral Fellow
Sandra Bonache

Radiation Oncologist
Manuel Altabas

Graduate Student
Gemma Montalban

Technicians
Vanessa Bach
Anna Tenés

Summary / Oncogenetics Group

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 mainly by BRCA1, BRCA2, PALB2, RAD51C, TP53, as well as some other genes. We search for other alleles that may predispose to these types of cancer using massive sequencing technologies to study panels of potentially predisposing genes. Moreover, we analyze whole exomes to discover new genes that could explain the presence of multiple cancers in families and individual patients.

BRCA1/2 genes have an extraordinary high allelic heterogeneity and many results of genetic testing are variants with unknown clinical significance (VUS). The analysis of these variants and other alterations in untranslated regions in both genes constitutes another area of intensive study. We carry out splicing studies, in silico analyses, and collaborate with other partners in international consortia (ENIGMA) to develop multifactorial studies aimed at ascertaining the effect of VUS. We are also working to establish a biological model through which to evaluate the in vitro functional effect of VUS and determine their potential pathogenicity.

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

During 2015, we initiated a project (PI: Cristina Cruz) in collaboration with VHIO’s High Risk & Cancer Prevention and Experimental Therapeutics Groups, headed by Judith Balmaña and Violeta Serra respectively, 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 at some point during the course of their treatment and between 3-5% of these patients suffer from severe long-term side-effects. Current evidence suggests the heritability of radiosensitivity, triggering growing interest in identifying the genetic variants associated with increased sensitivity to radiation. To identify those patients who will develop toxicity, we are investigating potential genetic and cellular markers for radiotherapy toxicity (allelic variants, cell apoptosis, and transcriptional profiles). In collaboration with the International Consortium of Radiogenomics we have participated in a meta-analysis showing an association between the ATM rs1801516 SNP and toxicity post-radiotherapy.

Strategic Goals / Oncogenetics Group

  1. Application of massive sequencing to the diagnosis of hereditary cancer.
  2. Identification of new alleles for genetic predisposition to breast/ovarian cancer.
  3. Expression and functional analysis of genetic variants with unknown clinical significance in familiar cancer predisposition.
  4. Identification of common low-penetrance alleles that modify breast/ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.
  5. Study of apoptosis assay and genetic markers as predictive tests for late toxicity after radiotherapy.
  6. Assess the role of microRNAs and long non coding RNAs in the susceptibility to radiotherapy-induced clinical toxicity.

Highlights 2015 / Oncogenetics Group

  1. Exome sequence analysis of breast cancer families negative for BRCA1/2 to unmask new potential predisposing genes, and involvement in the COMPLEXO Consortium to identify the missing heritability of breast cancer via exorne studies.
  2. Our group has analyzed an extensive panel of cancer genes by massive sequencing, and revealed new predisposing alleles in affected families.
  3. Participation in a multicenter study to determine the association of variants in the FANCM gene to breast cancer predisposition.
  4. In partnership with the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), we have described new susceptibility genes of ovarian cancer and modifier alleles for BRCA1/BRCA2 mutation carriers.
  5. Our confirmation that severe, late side effects induced by breast cancer radiotherapy are associated with low levels of irradiation-induced apoptosis.
  6. The enrolment of breast cancer patients in the European Commission FP7-funded project REQUITE to validate predictive models of toxicity from radiotherapy.

PI Paper Pick / Oncogenetics Group

Fuentes-Raspall MJ, Caragol I, Alonso C, Ramón Y Cajal T, Fisas D, Seoane A, Carvajal N, Bonache S, Díez O, Gutiérrez-Enríquez S. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism. Apoptosis. 2015;20(3):371-382.

Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, …, the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nat Genet. 2015;47(2):164-171.

Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA. 2015;313(13):1347-1361.

Eccles D, Mitchell G, Monteiro ANA, Schmutzler R, Couch FJ, Spurdle AS, Gómez-García EB, on behalf of the ENIGMA Clinical Working Group. BRCA1 and BRCA2 genetic testing – pitfalls and recommendations for managing variants of uncertain clinical significance. Ann Oncol. 2015;26(10):2057-2065.

Horizons 2016 / Oncogenetics Group

  1. Bioinformatic analysis of exome sequencing of families with multiple cases of breast cancer at a young age to detect putative cancer predisposition mutations.
  2. Identification and functional characterization of genetic variants located deep intronic or in untranslated regions of BRCA1, BRCA2 and other genes.
  3. Assess the potential pathogenicity and functional significance of BRCA1 and BRCA2 transcripts using semi-quantitative and quantitative assays.
  4. Validation of a new in silico algorithm to analyze the effect on protein function of variants of unknown biological significance in BRCA1 and BRCA2 genes.
  5. Identification of new low penetrance breast and ovarian cancer susceptibility genes and risk modifier genes for BRCA1 and BRCA2, collaborating with the CIMBA Consortium.
  6. Identification of BRCA mRNA isoforms as a potential novel mechanism of resistance against PARP inhibitors.
  7. Participation in a European project (REQUITE) with a prospective cohort of breast and lung cancer patients treated with radiotherapy, collecting toxicity data, non-genetic risk factors and DNA/RNA samples for biomarker assays of radiotherapy side-effects.
  8. Identification of susceptibility genetic variants in microRNAs and long non-coding RNAs related to radiotherapy-induced clinical toxicity.

Publications / Oncogenetics Group

  1. Peterlongo P, Chang-Claude J, Moysich KB, Rudolph A, Schmutzler RK, Simard J, Soucy P, Eeles RA, Easton DF, Hamann U, Wilkening S, Chen B, Rookus MA, Schmidt MK, van der Baan FH, Spurdle AB, Walker LC, Lose F, Maia AT, Montagna M, Matricardi L, Lubinski J, Jakubowska A, Gomez-Garcia EB, Olopade OI, Nussbaum RL, Nathanson KL, Domchek SM, Rebbeck TR, Arun BK, Karlan BY, Orsulic S, Lester J, Chung WK, Miron A, Southey MC, Goldgar DE, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Ding YC, Neuhausen SL, Hansen TV, Gerdes AM, Ejlertsen B, Jønson L, Osorio A, Martinez-Bouzas C, Benitez J, Conway EE, Blazer KR, Weitzel JN, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Barile M, Ficarazzi F, Mariette F, Fortuzzi S, Viel A, Giannini G, Papi L, Martayan A, Tibiletti MG, Radice P, Vratimos A, Fostira F, Garber JE, Donaldson A, Brewer C, Foo C, Evans DG, Frost D, Eccles D, Brady A, Cook J, Tischkowitz M, Adlard J, Barwell J, Walker L, Izatt L, Side LE, Kennedy MJ, Rogers MT, Porteous ME, Morrison PJ, Platte R, Davidson R, Hodgson SV, Ellis S, Cole T, Godwin AK, Claes K, Van Maerken T, Meindl A, Gehrig A, Sutter C, Engel C, Niederacher D, Steinemann D, Plendl H, Kast K, Rhiem K, Ditsch N, Arnold N, Varon-Mateeva R, Wappenschmidt B, Wang-Gohrke S, Bressac-de Paillerets B, Buecher B, Delnatte C, Houdayer C, Stoppa-Lyonnet D, Damiola F, Coupier I, Barjhoux L, Venat-Bouvet L, Golmard L, Boutry-Kryza N, Sinilnikova OM, Caron O, Pujol P, Mazoyer S, Belotti M, Piedmonte M, Friedlander ML, Rodriguez GC, Copeland LJ, de la Hoya M, Perez Segura P, Nevanlinna H, Aittomäki K, van Os TA, Meijers-Heijboer HE, Van der Hout AH, Vreeswijk MP, Hoogerbrugge N, Ausems MG, Van Doorn HC, Collée JM, Olah E, Díez O, Blanco I, Lazaro C, Brunet J, Feliubadaló L, Cybulski C, Gronwald J, Durda K, Jaworska-Bieniek K, Sukiennicki G, Arason A, Chiquette J, Teixeira MR, Olswold C, Couch FJ, Lindor NM, Wang X, Szabo CI, Offit K, Corines M, Jacobs L, Robson M, Zhang L, Joseph V, Berger A, Singer CF, Rappaport C, Geschwantler Kaulich D, Pfeiler G, Tea MK, Phelan CM, Greene MH, Mai PL, Rennert G, Mulligan AM, Glendon G, Tchatchou S, Andrulis IL, Toland AE, Bojesen A, Pedersen IS, Thomassen M, Jensen UB, Laitman Y, Rantala J, von Wachenfeldt A, Ehrencrona H, Stenmark Askmalm M, Borg A, Kuchenbaecker KB, McGuffog L, Barrowdale D, Healey S, Lee A, Pharoah PD, Chenevix-Trench G On Behalf Of Aocs Mamagement Group, Antoniou AC, Friedman E. Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 2015;24:308-16.
  2. Fuentes-Raspall MJ, Caragol I, Alonso C, Ramón Y Cajal T, Fisas D, Seoane A, Carvajal N, Bonache S, Díez O, Gutiérrez-Enríquez S. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism. Apoptosis 2015;20:371-82.
  3. Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, Lawrenson K, McGuffog L, Healey S, Lee JM, Spindler TJ, Lin YG, Pejovic T, Bean Y, Li Q, Coetzee S, Hazelett D, Miron A, Southey M, Terry MB, Goldgar DE, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Neuhausen SL, Ding YC, Hansen TV, Jønson L, Gerdes AM, Ejlertsen B, Barrowdale D, Dennis J, Benitez J, Osorio A, Garcia MJ, Komenaka I, Weitzel JN, Ganschow P, Peterlongo P, Bernard L, Viel A, Bonanni B, Peissel B, Manoukian S, Radice P, Papi L, Ottini L, Fostira F, Konstantopoulou I, Garber J, Frost D, Perkins J, Platte R, Ellis S; EMBRACE, Godwin AK, Schmutzler RK, Meindl A, Engel C, Sutter C, Sinilnikova OM; GEMO Study Collaborators, Damiola F, Mazoyer S, Stoppa-Lyonnet D, Claes K, De Leeneer K, Kirk J, Rodriguez GC, Piedmonte M, O'Malley DM, de la Hoya M, Caldes T, Aittomäki K, Nevanlinna H, Collée JM, Rookus MA, Oosterwijk JC; Breast Cancer Family Registry, Tihomirova L, Tung N, Hamann U, Isaccs C, Tischkowitz M, Imyanitov EN, Caligo MA, Campbell IG, Hogervorst FB; HEBON, Olah E, Diez O, Blanco I, Brunet J, Lazaro C, Pujana MA, Jakubowska A, Gronwald J, Lubinski J, Sukiennicki G, Barkardottir RB, Plante M, Simard J, Soucy P, Montagna M, Tognazzo S, Teixeira MR;KConFab Investigators, Pankratz VS, Wang X, Lindor N, Szabo CI, Kauff N, Vijai J, Aghajanian CA, Pfeiler G, Berger A, Singer CF, Tea MK, Phelan CM, Greene MH, Mai PL, Rennert G, Mulligan AM, Tchatchou S, Andrulis IL, Glendon G, Toland AE, Jensen UB, Kruse TA, Thomassen M, Bojesen A, Zidan J, Friedman E, Laitman Y, Soller M, Liljegren A, Arver B, Einbeigi Z, Stenmark-Askmalm M, Olopade OI, Nussbaum RL, Rebbeck TR, Nathanson KL, Domchek SM, Lu KH, Karlan BY, Walsh C, Lester J; Australian Cancer Study (Ovarian Cancer Investigators); Australian Ovarian Cancer Study Group, Hein A, Ekici AB, Beckmann MW, Fasching PA, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambrechts S, Dicks E, Doherty JA, Wicklund KG, Rossing MA, Rudolph A, Chang-Claude J, Wang-Gohrke S, Eilber U, Moysich KB, Odunsi K, Sucheston L, Lele S, Wilkens LR, Goodman MT, Thompson PJ, Shvetsov YB, Runnebaum IB, Dürst M, Hillemanns P, Dörk T, Antonenkova N, Bogdanova N, Leminen A, Pelttari LM, Butzow R, Modugno F, Kelley JL, Edwards RP, Ness RB, du Bois A, Heitz F, Schwaab I, Harter P, Matsuo K, Hosono S, Orsulic S, Jensen A, Kjaer SK, Hogdall E, Hasmad HN, Azmi MA, Teo SH, Woo YL, Fridley BL, Goode EL, Cunningham JM, Vierkant RA, Bruinsma F, Giles GG, Liang D, Hildebrandt MA, Wu X, Levine DA, Bisogna M, Berchuck A, Iversen ES, Schildkraut JM, Concannon P, Weber RP, Cramer DW, Terry KL, Poole EM, Tworoger SS, Bandera EV, Orlow I, Olson SH, Krakstad C, Salvesen HB, Tangen IL, Bjorge L, van Altena AM, Aben KK, Kiemeney LA, Massuger LF, Kellar M, Brooks-Wilson A, Kelemen LE, Cook LS, Le ND, Cybulski C, Yang H, Lissowska J, Brinton LA, Wentzensen N, Hogdall C, Lundvall L, Nedergaard L, Baker H, Song H, Eccles D, McNeish I, Paul J, Carty K, Siddiqui N, Glasspool R, Whittemore AS, Rothstein JH, McGuire V, Sieh W, Ji BT, Zheng W, Shu XO, Gao YT, Rosen B, Risch HA, McLaughlin JR, Narod SA, Monteiro AN, Chen A, Lin HY, Permuth-Wey J, Sellers TA, Tsai YY, Chen Z, Ziogas A, Anton-Culver H, Gentry-Maharaj A, Menon U, Harrington P, Lee AW, Wu AH, Pearce CL, Coetzee G, Pike MC, Dansonka-Mieszkowska A, Timorek A, Rzepecka IK, Kupryjanczyk J, Freedman M, Noushmehr H, Easton DF, Offit K, Couch FJ, Gayther S, Pharoah PP, Antoniou AC, Chenevix-Trench G; the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nat Genet 2015;47:164-71.
  4. Blanco I, Kuchenbaecker K, Cuadras D, Wang X, Barrowdale D, de Garibay GR, Librado P, Sánchez-Gracia A, Rozas J, Bonifaci N, McGuffog L, Pankratz VS, Islam A, Mateo F, Berenguer A, Petit A, Català I, Brunet J, Feliubadaló L, Tornero E, Benítez J, Osorio A, Cajal TR, Nevanlinna H, Aittomäki K, Arun BK, Toland AE, Karlan BY, Walsh C, Lester J, Greene MH, Mai PL, Nussbaum RL, Andrulis IL, Domchek SM, Nathanson KL, Rebbeck TR, Barkardottir RB, Jakubowska A, Lubinski J, Durda K, Jaworska-Bieniek K, Claes K, Van Maerken T, Díez O, Hansen TV, Jønson L, Gerdes AM, Ejlertsen B, de la Hoya M, Caldés T, Dunning AM, Oliver C, Fineberg E, Cook M, Peock S, McCann E, Murray A, Jacobs C, Pichert G, Lalloo F, Chu C, Dorkins H, Paterson J, Ong KR, Teixeira MR; Teixeira, Hogervorst FB, van der Hout AH, Seynaeve C, van der Luijt RB, Ligtenberg MJ, Devilee P, Wijnen JT, Rookus MA, Meijers-Heijboer HE, Blok MJ, van den Ouweland AM, Aalfs CM, Rodriguez GC, Phillips KA, Piedmonte M, Nerenstone SR, Bae-Jump VL, O'Malley DM, Ratner ES, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, Meindl A, Ditsch N, Arnold N, Plendl HJ, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Gehrig A, Bojesen A, Pedersen IS, Sunde L, Jensen UB, Thomassen M, Kruse TA, Foretova L, Peterlongo P, Bernard L, Peissel B, Scuvera G, Manoukian S, Radice P, Ottini L, Montagna M, Agata S, Maugard C, Simard J, Soucy P, Berger A, Fink-Retter A, Singer CF, Rappaport C, Geschwantler-Kaulich D, Tea MK, Pfeiler G; BCFR, John EM, Miron A, Neuhausen SL, Terry MB, Chung WK, Daly MB, Goldgar DE, Janavicius R, Dorfling CM, van Rensburg EJ, Fostira F, Konstantopoulou I, Garber J, Godwin AK, Olah E, Narod SA, Rennert G, Paluch SS, Laitman Y, Friedman E; SWE-BRCA, Liljegren A, Rantala J, Stenmark-Askmalm M, Loman N, Imyanitov EN, Hamann U; kConFab Investigators, Spurdle AB, Healey S, Weitzel JN, Herzog J, Margileth D, Gorrini C, Esteller M, Gómez A, Sayols S, Vidal E, Heyn H; GEMO, Stoppa-Lyonnet D, Léoné M, Barjhoux L, Fassy-Colcombet M, de Pauw A, Lasset C, Ferrer SF, Castera L, Berthet P, Cornelis F, Bignon YJ, Damiola F, Mazoyer S, Sinilnikova OM, Maxwell CA, Vijai J, Robson M, Kauff N, Corines MJ, Villano D, Cunningham J, Lee A, Lindor N, Lázaro C, Easton DF, Offit K, Chenevix-Trench G, Couch FJ, Antoniou AC, Pujana MA. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers. PLoS One. 2015 Apr 1;10(4):e0120020.
  5. Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, Mazoyer S, Chenevix-Trench G, Easton DF, Antoniou AC, Nathanson KL; and the CIMBA Consortium, Laitman Y, Kushnir A, Paluch-Shimon S, Berger R, Zidan J, Friedman E, Ehrencrona H, Stenmark-Askmalm M, Einbeigi Z, Loman N, Harbst K, Rantala J, Melin B, Huo D, Olopade OI, Seldon J, Ganz PA, Nussbaum RL, Chan SB, Odunsi K, Gayther SA, Domchek SM, Arun BK, Lu KH, Mitchell G, Karlan BY, Walsh C, Lester J, Godwin AK, Pathak H, Ross E, Daly MB, Whittemore AS, John EM, Miron A, Terry MB, Chung WK, Goldgar DE, Buys SS, Janavicius R, Tihomirova L, Tung N, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Ejlertsen B, Gerdes AM, Hansen TV, Ramón Y Cajal T, Osorio A, Benitez J, Godino J, Tejada MI, Duran M, Weitzel JN, Bobolis KA, Sand SR, Fontaine A, Savarese A, Pasini B, Peissel B, Bonanni B, Zaffaroni D, Vignolo-Lutati F, Scuvera G, Giannini G, Bernard L, Genuardi M, Radice P, Dolcetti R, Manoukian S, Pensotti V, Gismondi V, Yannoukakos D, Fostira F, Garber J, Torres D, Rashid MU, Hamann U, Peock S, Frost D, Platte R, Evans DG, Eeles R, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Hodgson S, Morrison PJ, Walker L, Porteous ME, Kennedy MJ, Izatt L, Adlard J, Donaldson A, Ellis S, Sharma P, Schmutzler RK, Wappenschmidt B, Becker A, Rhiem K, Hahnen E, Engel C, Meindl A, Engert S, Ditsch N, Arnold N, Plendl HJ, Mundhenke C, Niederacher D, Fleisch M, Sutter C, Bartram CR, Dikow N, Wang-Gohrke S, Gadzicki D, Steinemann D, Kast K, Beer M, Varon-Mateeva R, Gehrig A, Weber BH, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Houdayer C, Belotti M, Gauthier-Villars M, Damiola F, Boutry-Kryza N, Lasset C, Sobol H, Peyrat JP, Muller D, Fricker JP, Collonge-Rame MA, Mortemousque I, Nogues C, Rouleau E, Isaacs C, De Paepe A, Poppe B, Claes K, De Leeneer K, Piedmonte M, Rodriguez G, Wakely K, Boggess J, Blank SV, Basil J, Azodi M, Phillips KA, Caldes T, de la Hoya M, Romero A, Nevanlinna H, Aittomäki K, van der Hout AH, Hogervorst FB, Verhoef S, Collée JM, Seynaeve C, Oosterwijk JC, Gille JJ, Wijnen JT, Garcia EB, Kets CM, Ausems MG, Aalfs CM, Devilee P, Mensenkamp AR, Kwong A, Olah E, Papp J, Diez O, Lazaro C, Darder E, Blanco I, Salinas M, Jakubowska A, Lubinski J, Gronwald J, Jaworska-Bieniek K, Durda K, Sukiennicki G, Huzarski T, Byrski T, Cybulski C, Toloczko-Grabarek A, Zlowocka-Perlowska E, Menkiszak J, Arason A, Barkardottir RB, Simard J, Laframboise R, Montagna M, Agata S, Alducci E, Peixoto A, Teixeira MR, Spurdle AB, Lee MH, Park SK, Kim SW, Friebel TM, Couch FJ, Lindor NM, Pankratz VS, Guidugli L, Wang X, Tischkowitz M, Foretova L, Vijai J, Offit K, Robson M, Rau-Murthy R, Kauff N, Fink-Retter A, Singer CF, Rappaport C, Gschwantler-Kaulich D, Pfeiler G, Tea MK, Berger A, Greene MH, Mai PL, Imyanitov EN, Toland AE, Senter L, Bojesen A, Pedersen IS, Skytte AB, Sunde L, Thomassen M, Moeller ST, Kruse TA, Jensen UB, Caligo MA, Aretini P, Teo SH, Selkirk CG, Hulick PJ, Andrulis I. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA 2015;313:1347-1361.
  6. Blein S, Bardel C, Danjean V, McGuffog L, Healey S, Barrowdale D, Lee A, Dennis J, Kuchenbaecker KB, Soucy P, Terry MB, Chung WK, Goldgar DE, Buys SS; BCFR, Janavicius R, Tihomirova L, Tung N, Dorfling CM, van Rensburg EJ, Neuhausen SL, Ding YC, Gerdes AM, Ejlertsen B, Nielsen FC, Hansen TV, Osorio A, Benitez J, Andrés-Conejero R, Segota E, Weitzel JN, Thelander M, Peterlongo P, Radice P, Pensotti V, Dolcetti R, Bonanni B, Peissel B, Zaffaroni D, Scuvera G, Manoukian S, Varesco L, Capone GL, Papi L, Ottini L, Yannoukakos D, Konstantopoulou I, Garber J, Hamann U, Donaldson A, Brady A, Brewer C, Foo C, Evans DG, Frost D, Eccles D; EMBRACE, Douglas F, Cook J, Adlard J, Barwell J, Walker L, Izatt L, Side LE, Kennedy MJ, Tischkowitz M, Rogers MT, Porteous ME, Morrison PJ, Platte R, Eeles R, Davidson R, Hodgson S, Cole T, Godwin AK, Isaacs C, Claes K, De Leeneer K, Meindl A, Gehrig A, Wappenschmidt B, Sutter C, Engel C, Niederacher D, Steinemann D, Plendl H, Kast K, Rhiem K, Ditsch N, Arnold N, Varon-Mateeva R, Schmutzler RK, Preisler-Adams S, Markov NB, Wang-Gohrke S, de Pauw A, Lefol C, Lasset C, Leroux D, Rouleau E, Damiola F; GEMO Study Collaborators, Dreyfus H, Barjhoux L, Golmard L, Uhrhammer N, Bonadona V, Sornin V, Bignon YJ, Carter J, Van Le L, Piedmonte M, DiSilvestro PA, de la Hoya M, Caldes T, Nevanlinna H, Aittomäki K, Jager A, van den Ouweland AM, Kets CM, Aalfs CM, van Leeuwen FE, Hogervorst FB, Meijers-Heijboer HE; HEBON, Oosterwijk JC, van Roozendaal KE, Rookus MA, Devilee P, van der Luijt RB, Olah E, Diez O, Teulé A, Lazaro C, Blanco I, Del Valle J, Jakubowska A, Sukiennicki G, Gronwald J, Lubinski J, Durda K, Jaworska-Bieniek K, Agnarsson BA, Maugard C, Amadori A, Montagna M, Teixeira MR, Spurdle AB, Foulkes W, Olswold C, Lindor N, Pankratz VS, Szabo CI, Lincoln A, Jacobs L, Corines M, Robson M, Vijai J, Berger A, Fink-Retter A, Singer CF, Rappaport C, Kaulich DG, Pfeiler G, Tea MK, Greene MH, Mai PL, Rennert G, Imyanitov EN, Mulligan AM, Glendon G, Andrulis IL, Tchatchou S, Toland AE, Pedersen IS, Thomassen M, Kruse TA, Jensen UB, Caligo MA, Friedman E, Zidan J, Laitman Y, Lindblom A, Melin B, Arver B, Loman N, Rosenquist R, Olopade OI, Nussbaum RL, Ramus SJ, Nathanson KL, Domchek SM, Rebbeck TR, Arun BK, Mitchell G, Karlan BY, Lester J, Orsulic S, Stoppa-Lyonnet D, Thomas G, Simard J, Couch FJ, Offit K, Easton DF, Chenevix-Trench G, Antoniou AC, Mazoyer S, Phelan CM, Sinilnikova OM, Cox DG. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers. Breast Cancer Res 2015;17:61.
  7. Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2, Hollestelle A, van der Baan FH, Berchuck A, Johnatty SE, Aben KK, Agnarsson BA, Aittomäki K, Alducci E, Andrulis IL, Anton-Culver H, Antonenkova NN, Antoniou AC, Apicella C, Arndt V, Arnold N, Arun BK, Arver B, Ashworth A; Australian Ovarian Cancer Study Group, Baglietto L, Balleine R, Bandera EV, Barrowdale D, Bean YT, Beckmann L, Beckmann MW, Benitez J, Berger A, Berger R, Beuselinck B, Bisogna M, Bjorge L, Blomqvist C, Bogdanova NV, Bojesen A, Bojesen SE, Bolla MK, Bonanni B, Brand JS, Brauch H; Breast Cancer Family Register, Brenner H, Brinton L, Brooks-Wilson A, Bruinsma F, Brunet J, Brüning T, Budzilowska A, Bunker CH, Burwinkel B, Butzow R, Buys SS, Caligo MA, Campbell I, Carter J, Chang-Claude J, Chanock SJ, Claes KB, Collée JM, Cook LS, Couch FJ, Cox A, Cramer D, Cross SS, Cunningham JM, Cybulski C, Czene K, Damiola F, Dansonka-Mieszkowska A, Darabi H, de la Hoya M, deFazio A, Dennis J, Devilee P, Dicks EM, Diez O, Doherty JA, Domchek SM, Dorfling CM, Dörk T, Silva ID, du Bois A, Dumont M, Dunning AM, Duran M, Easton DF, Eccles D, Edwards RP, Ehrencrona H, Ejlertsen B, Ekici AB, Ellis SD; EMBRACE, Engel C, Eriksson M, Fasching PA, Feliubadalo L, Figueroa J, Flesch-Janys D, Fletcher O, Fontaine A, Fortuzzi S, Fostira F, Fridley BL, Friebel T, Friedman E, Friel G, Frost D, Garber J, García-Closas M, Gayther SA; GEMO Study Collaborators; GENICA Network, Gentry-Maharaj A, Gerdes AM, Giles GG, Glasspool R, Glendon G, Godwin AK, Goodman MT, Gore M, Greene MH, Grip M, Gronwald J, Gschwantler Kaulich D, Guénel P, Guzman SR, Haeberle L, Haiman CA, Hall P, Halverson SL, Hamann U, Hansen TV, Harter P, Hartikainen JM, Healey S; HEBON, Hein A, Heitz F, Henderson BE, Herzog J, T Hildebrandt MA, Høgdall CK, Høgdall E, Hogervorst FB, Hopper JL, Humphreys K, Huzarski T, Imyanitov EN, Isaacs C, Jakubowska A, Janavicius R, Jaworska K, Jensen A, Jensen UB, Johnson N, Jukkola-Vuorinen A, Kabisch M, Karlan BY, Kataja V, Kauff N; KConFab Investigators, Kelemen LE, Kerin MJ, Kiemeney LA, Kjaer SK, Knight JA, Knol-Bout JP, Konstantopoulou I, Kosma VM, Krakstad C, Kristensen V, Kuchenbaecker KB, Kupryjanczyk J, Laitman Y, Lambrechts D, Lambrechts S, Larson MC, Lasa A, Laurent-Puig P, Lazaro C, Le ND, Le Marchand L, Leminen A, Lester J, Levine DA, Li J, Liang D, Lindblom A, Lindor N, Lissowska J, Long J, Lu KH, Lubinski J, Lundvall L, Lurie G, Mai PL, Mannermaa A, Margolin S, Mariette F, Marme F, Martens JW, Massuger LF, Maugard C, Mazoyer S, McGuffog L, McGuire V, McLean C, McNeish I, Meindl A, Menegaux F, Menéndez P, Menkiszak J, Menon U, Mensenkamp AR, Miller N, Milne RL, Modugno F, Montagna M, Moysich KB, Müller H, Mulligan AM, Muranen TA, Narod SA, Nathanson KL, Ness RB, Neuhausen SL, Nevanlinna H, Neven P, Nielsen FC, Nielsen SF, Nordestgaard BG, Nussbaum RL, Odunsi K, Offit K, Olah E, Olopade OI, Olson JE, Olson SH, Oosterwijk JC, Orlow I, Orr N, Orsulic S, Osorio A, Ottini L, Paul J, Pearce CL, Pedersen IS, Peissel B, Pejovic T, Pelttari LM, Perkins J, Permuth-Wey J, Peterlongo P, Peto J, Phelan CM, Phillips KA, Piedmonte M, Pike MC, Platte R, Plisiecka-Halasa J, Poole EM, Poppe B, Pylkäs K, Radice P, Ramus SJ, Rebbeck TR, Reed MW, Rennert G, Risch HA, Robson M, Rodriguez GC, Romero A, Rossing MA, Rothstein JH, Rudolph A, Runnebaum I, Salani R, Salvesen HB, Sawyer EJ, Schildkraut JM, Schmidt MK, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schrauder MG, Schumacher F, Schwaab I, Scuvera G, Sellers TA, Severi G, Seynaeve CM, Shah M, Shrubsole M, Siddiqui N, Sieh W, Simard J, Singer CF, Sinilnikova OM, Smeets D, Sohn C, Soller M, Song H, Soucy P, Southey MC, Stegmaier C, Stoppa-Lyonnet D, Sucheston L; SWE-BRCA, Swerdlow A, Tangen IL, Tea MK, Teixeira MR, Terry KL, Terry MB, Thomassen M, Thompson PJ, Tihomirova L, Tischkowitz M, Toland AE, Tollenaar RA, Tomlinson I, Torres D, Truong T, Tsimiklis H, Tung N, Tworoger SS, Tyrer JP, Vachon CM, Van 't Veer LJ, van Altena AM, Van Asperen CJ, van den Berg D, van den Ouweland AM, van Doorn HC, Van Nieuwenhuysen E, van Rensburg EJ, Vergote I, Verhoef S, Vierkant RA, Vijai J, Vitonis AF, von Wachenfeldt A, Walsh C, Wang Q, Wang-Gohrke S, Wappenschmidt B, Weischer M, Weitzel JN, Weltens C, Wentzensen N, Whittemore AS, Wilkens LR, Winqvist R, Wu AH, Wu X, Yang HP, Zaffaroni D, Pilar Zamora M, Zheng W, Ziogas A, Chenevix-Trench G, Pharoah PD, Rookus MA, Hooning MJ, Goode EL. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecol Oncol. 2015 May 2. pii: S0090-8258(15)00863-X.
  8. de Juan I, Palanca S, Domenech A, Feliubadaló L, Segura A, Osorio A, Chirivella I, de la Hoya M, Sánchez AB, Infante M, Tena I, Díez O, Garcia-Casado Z, Vega A, Teulé A, Barroso A, Pérez P, Durán M, Carrasco E, Juan-Fita MJ, Murria R, Llop M, Barragan E, Izquierdo A, Benítez J, Caldés T, Salas D, Bolufer P. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Fam Cancer 2015;14:505-13
  9. Peterlongo P, Catucci I, Colombo M, Caleca L, Mucaki E, Bogliolo M, Marin M, Damiola F, Bernard L, Pensotti V, Volorio S, Dall'Olio V, Meindl A, Bartram C, Sutter C, Surowy H, Sornin V, Dondon MG, Eon-Marchais S, Stoppa-Lyonnet D, Andrieu N, Sinilnikova OM; GENESIS, Mitchell G, James PA, Thompson E; kConFab; SWE-BRCA, Marchetti M, Verzeroli C, Tartari C, Capone G, Putignano AL, Genuardi M, Medici V, Marchi I, Federico M, Tognazzo S, Matricardi L, Agata S, Dolcetti R, Della Puppa L, Cini G, Gismondi V, Viassolo V, Perfumo C, Mencarelli MA, Baldassarri M, Peissel B, Roversi G, Silvestri V, Rizzolo P, Spina F, Vivanet C, Tibiletti MG, Caligo MA, Gambino G, Tommasi S, Pilato B, Tondini C, Corna C, Bonanni B, Barile M, Osorio A, Benitez J, Balestrino L, Ottini L, Manoukian S, Pierotti MA, Renieri A, Varesco L, Couch FJ, Wang X, Devilee P, Hilbers FS, van Asperen CJ, Viel A, Montagna M, Cortesi L, Diez O, Balmaña J, Hauke J, Schmutzler RK, Papi L, Pujana MA, Lázaro C, Falanga A, Offit K, Vijai J, Campbell I, Burwinkel B, Kvist A, Ehrencrona H, Mazoyer S, Pizzamiglio S, Verderio P, Surralles J, Rogan PK, Radice P. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity, and is a familial breast cancer risk factor. Hum Mol Genet 2015;24:5345-55.
  10. Eccles D, Mitchell G, Monteiro ANA, Schmutzler R, Couch FJ, Spurdle AS, Gómez-García EB, on behalf of the ENIGMA Clinical Working Group. BRCA1 and BRCA2 genetic testing pitfalls and recommendations for managing variants of uncertain clinical significance. Ann Oncol 2015; 26:2057-65.
  11. Meeks HD, Song H, Michailidou K, Bolla MK, Dennis J, Wang Q, Barrowdale D, Frost D; EMBRACE, McGuffog L, Ellis S, Feng B, Buys SS, Hopper JL, Southey MC, Tesoriero A; kConFab Investigators, James PA, Bruinsma F, Campbell IG; Australia Ovarian Cancer Study Group, Broeks A, Schmidt MK, Hogervorst FB; HEBON, Beckman MW, Fasching PA, Fletcher O, Johnson N, Sawyer EJ, Riboli E, Banerjee S, Menon U, Tomlinson I, Burwinkel B, Hamann U, Marme F, Rudolph A, Janavicius R, Tihomirova L, Tung N, Garber J, Cramer D, Terry KL, Poole EM, Tworoger SS, Dorfling CM, van Rensburg EJ, Godwin AK, Guénel P, Truong T; GEMO Study Collaborators, Stoppa-Lyonnet D, Damiola F, Mazoyer S, Sinilnikova OM, Isaacs C, Maugard C, Bojesen SE, Flyger H, Gerdes AM, Hansen TV, Jensen A, Kjaer SK, Hogdall C, Hogdall E, Pedersen IS, Thomassen M, Benitez J, González-Neira A, Osorio A, Hoya Mde L, Segura PP, Diez O, Lazaro C, Brunet J, Anton-Culver H, Eunjung L, John EM, Neuhausen SL, Ding YC, Castillo D, Weitzel JN, Ganz PA, Nussbaum RL, Chan SB, Karlan BY, Lester J, Wu A, Gayther S, Ramus SJ, Sieh W, Whittermore AS, Monteiro AN, Phelan CM, Terry MB, Piedmonte M, Offit K, Robson M, Levine D, Moysich KB, Cannioto R, Olson SH, Daly MB, Nathanson KL, Domchek SM, Lu KH, Liang D, Hildebrant MA, Ness R, Modugno F, Pearce L, Goodman MT, Thompson PJ, Brenner H, Butterbach K, Meindl A, Hahnen E, Wappenschmidt B, Brauch H, Brüning T, Blomqvist C, Khan S, Nevanlinna H, Pelttari LM, Aittomäki K, Butzow R, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Rantala J, Kosma VM, Mannermaa A, Lambrechts D, Neven P, Claes KB, Maerken TV, Chang-Claude J, Flesch-Janys D, Heitz F, Varon-Mateeva R, Peterlongo P, Radice P, Viel A, Barile M, Peissel B, Manoukian S, Montagna M, Oliani C, Peixoto A, Teixeira MR, Collavoli A, Hallberg E, Olson JE, Goode EL, Hart SN, Shimelis H, Cunningham JM, Giles GG, Milne RL, Healey S, Tucker K, Haiman CA, Henderson BE, Goldberg MS, Tischkowitz M, Simard J, Soucy P, Eccles DM, Le N, Borresen-Dale AL, Kristensen V, Salvesen HB, Bjorge L, Bandera EV, Risch H, Zheng W, Beeghly-Fadiel A, Cai H, Pylkäs K, Tollenaar RA, Ouweland AM, Andrulis IL, Knight JA; OCGN, Narod S, Devilee P, Winqvist R, Figueroa J, Greene MH, Mai PL, Loud JT, García-Closas M, Schoemaker MJ, Czene K, Darabi H, McNeish I, Siddiquil N, Glasspool R, Kwong A, Park SK, Teo SH, Yoon SY, Matsuo K, Hosono S, Woo YL, Gao YT, Foretova L, Singer CF, Rappaport-Feurhauser C, Friedman E, Laitman Y, Rennert G, Imyanitov EN, Hulick PJ, Olopade OI, Senter L, Olah E, Doherty JA, Schildkraut J, Koppert LB, Kiemeney LA, Massuger LF, Cook LS, Pejovic T, Li J, Borg A, Öfverholm A, Rossing MA, Wentzensen N, Henriksson K, Cox A, Cross SS, Pasini BJ, Shah M, Kabisch M, Torres D, Jakubowska A, Lubinski J, Gronwald J, Agnarsson BA, Kupryjanczyk J, Moes-Sosnowska J, Fostira F, Konstantopoulou I, Slager S, Jones M; PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome, Antoniou AC, Berchuck A, Swerdlow A, Chenevix-Trench G, Dunning AM, Pharoah PD, Hall P, Easton DF, Couch FJ, Spurdle AB, Goldgar DE.BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers. J Natl Cancer Inst 2015;108. pii: djv315

Projects / Oncogenetics Group

  1. Aplicación de la secuenciación masiva para la optimización del diagnóstico molecular del cáncer de mama y ovario hereditario
    Instituto de Salud Carlos III
    Principal Investigator: Orland Díez
    2012-2016
  2. Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality-of-life in cancer survivors-REQUITE” (Nº: 601826)
    EuropeanCommission FP7
    Local Principal Investigator: Sara Gutiérrez-Enríquez
    2013-2018
  1. Optimización del diagnóstico molecular del cáncer de mama y ovario hereditario:estudio de las variantes genéticas de efecto clínico desconocido en BRCA1 y BRCA2 mediante análisis funcionales y de transcripción y desarrollo de un nuevo predictor in silico
    Instituto de Salud Carlos III
    Principal Investigator: Sara Gutiérrez Enríquez
    2013-2016

Awards / Oncogenetics Group

Clinical Research Postdoctoral Fellowship
Recipient: Sandra Bonache
Agency: Fundación AECC Investigación contra el Cáncer
Duration: 2014-2017

Short-Stay Grant for visiting the Molecular Cancer Epidemiology group at QIMR Berghofer Medical Research Institute, Australia (head: Dr. Amanda Spurdle)
Recipient: Gemma Montalban
Agency: FundacióMontcelimar - Universitat de Barcelona
Duration: September 2015-November 2015

Oncology Data Science (ODysSey) Group / Rodrigo Dienstmann

Imagen

Principal Investigator
Rodrigo Dienstmann

Biostatistician
Marta Vilaró

Data Curators
Alba Meire
Fiorella Ruiz

Summary / Oncology Data Science (ODysSey) Group

VHIO’s Oncology Data Science (ODysSey) Group provides guidance to medical oncologists and cancer biologists during the development, validation and interpretation of “omics”-based tests that have direct clinical application. Our main objective is to provide researchers with reliable tools to investigate biomarkers developed to optimize patient stratification, based on differences in response patterns to cancer therapies or outcome.

To do so, we design and maintain clinical-molecular databases, integrating the results of “multi-omics” tumor profiling tests performed at VHIO with information available in electronic medical records, including treatment benefit and patient survival across multiple tumor types. This represents a critical resource for medical oncologists, molecular pathologists and translational investigators at VHIO studying predictive and prognostic biomarkers. We also manage the Gene Drug Knowledge Database (GDKD) (doi:10.7303/syn2370773), a structured database that uses standardized terminology to describe associations linking different layers of annotations: tumor types, genes, variants, response/resistance patterns to approved and experimental agents under clinical investigation, and PubMed identifiers.

We also encourage and promote collaborative research among computational oncology scientists on predictive and prognostic modeling, identification of cancer drivers, intra-tumor heterogeneity and druggability in solid tumors.

Strategic Goals / Oncology Data Science (ODysSey) Group

  1. Integration of clinical translational research with “omics” for precision cancer therapy.
  2. Clinical-molecular databases of matched targeted agents and immunotherapies.
  3. Standardized reports of next-generation sequencing tests.
  4. Collaborative research in cancer genomics/computational oncology and its clinical implications.

Highlights 2015 / Oncology Data Science (ODysSey) Group

  1. Participation in the European Consortium MedBioinformatics: our group was deeply involved in the development of integrative bioinformatics tools and autonomously usable software applications for scientists and clinical practitioners to analyze the huge amount of data and knowledge generated in healthcare and biomedical research in order to facilitate translational research and precision medicine.
  2. Our collaboration in the international Colorectal Cancer Subtyping Consortium: we were responsible for detailed characterization of the transcriptomic subtypes of colorectal cancer achieving consensus on newly defined molecular subgroups as published in Nature Medicine (Guinney J. et al. 2015. Nat Med. 21:1350-1356).
  3. Throughout 2015 we have led important advances in datamining, expert curation of the literature and knowledge interpretation of somatic gene alterations that have therapeutic impact in cancer, as published in Cancer Discovery (Dienstmann R. et al. Cancer Discov. 2015;5(2):118-23). Our Gene Drug Knowledge Database is publicly available and has become a reference for clinical investigators across the globe.
  4. Participation in the European Consortium MoTriColor: we had a critical role in the design of molecularly-guided clinical trials with specific targeted and immunotherapies for the newly defined colorectal cancer subgroups.

PI Paper Pick / Oncology Data Science (ODysSey) Group

Dienstmann R, Jang IS, Bot B, Friend S, Guinney J. Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. Cancer Discov. 2015;5(2):118-123.

Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol. 2015;33(16):1787-1796.

Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Roselló S, Tops BB, van der Post RS, Argilés G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J. Safety and activity of the first-in-class Sym004 anti-EGFR antibody mixture in patients with refractory colorectal cancer. Cancer Discov. 2015;5(6):598-609.

Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350-1356.

Horizons 2016 / Oncology Data Science (ODysSey) Group

  1. Design and implementation of data-sharing solutions across European institutions (the Cancer Core Europe Consortium) to maximise integration and functionality between existing rich cancer data sets and infrastructure for international collaborations.
  2. Research focusing on dynamic changes in the “omics” landscape of tumors with intervening therapies, clonality/subclonality of driver events and biomarkers for immunotherapy response.
  3. Development and exploration of tools that help translate the strong signals of biological dependencies of colorectal cancer subtypes into druggability in the clinical practice.

Publications / Oncology Data Science (ODysSey) Group

  1. Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. Dienstmann R, Jang IS, Bot B, Friend S, Guinney J. Cancer Discov. 2015;5(2):118-23.
  2. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. Dienstmann R, Salazar R, Tabernero J. J Clin Oncol. 2015; 33(16):1787-96.
  3. Safety and activity of the first-in-class Sym004 anti-EGFR antibody mixture in patients with refractory colorectal cancer. Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Roselló S, Tops BB, van der Post RS, Argilés G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J. Cancer Discov. 2015;5(6):598-609.
  4. The consensus molecular subtypes of colorectal cancer. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. Nat Med. 2015;21(11):1350-6.
  5. Stepwise group sparse regression (SGSR): gene-set-based pharmacogenomic predictive models with stepwise selection of functional priors. Jang IS, Dienstmann R, Margolin AA, Guinney J. Pac Symp Biocomput. 2015;20:32-43.
  6. Intrinsic cancer subtypes - next steps into personalized medicine. Santos C, Sanz-Pamplona R, Nadal E, Grasselli J, Pernas S, Dienstmann R, Moreno V, Tabernero J, Salazar R. Cell Oncol. (Dordr) 2015;38(1):3-16.
  7. Genomic testing in colorectal cancer: how much is enough? Dienstmann R, Salazar R, Tabernero J. Oncology (Williston Park) 2015;29(3):186-8.
  8. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Mau-Sørensen M, Dittrich C, Dienstmann R, Lassen U, Büchler W, Martinius H, Tabernero J. Cancer Chemother Pharmacol. 2015;75(5):1065-73.
  9. Heterogeneity of driver genes and therapeutic implications in colorectal cancer. Dienstmann R, Cervantes A. Annals Oncol. 2015;26(8):1523-5.
  10. Overcoming Resistance to anti-EGFR Therapy in Colorectal Cancer. Dienstmann R, Salazar R, Tabernero J. Am Soc Clin Oncol. Educ Book 2015;35:e149-56.
  11. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced solid tumors.Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit H, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria J-C. J Clin Oncol. 2015;33(30):3401-8.
  12. Tankyrase inhibition blocks Wnt/β-catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Arques O, Chicote I, Puig I, Tenbaum SP, Argiles G, Dienstmann R, Fernandez N, Caratu G, Matito J, Silberschmidt D, Rodon J, Landolfi S, Prat A, Espin E, Charco R, Nuciforo P, Vivancos A, Shao W, Tabernero J, Palmer HG. Clin Cancer Res. 2015;21(24):5499-510.

Projects / Oncology Data Science (ODysSey) Group

  1. Colorectal Cancer Subtyping Consortium
  2. MedBioinformatics
  3. MoTriColor

Radiation Oncology Group / Jordi Giralt

Imagen

Principal Investigator
Jordi Giralt

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

Summary / Radiation Oncology Group

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 as principal investigators or research collaborators in a number of important clinical trials, translational research projects, as well as technology development programs.

Current and future research priorities include the following key areas:

  • The continued implementation of IMRT in sarcoma, pediatric and gastrointestinal tumors.
  • Development of an estereotactic extracranial radiotherapy program in pancreas and bone metastases.
  • Develop a 4D program for lung cancer.
  • For breast cancer: the validation of partial breast irradiation in prone position technique.
  • The identification of factors associated with clinical response in advanced head and neck tumors treated with radiotherapy and chemotherapy or target therapies.
  • To seek the benefit of dose painting and adaptive radiotherapy in head and neck cancer in a clinical trial.
  • The use of nanoparticles as radiotherapy enhancement for soft tissue sarcomas.

Strategic Goals / Radiation Oncology Group

  1. Technology development: acquisition of new equipment to implement cutting edge clinical treatment techniques such as rotational radiotherapy - with intensity modulated arc therapy (IMAT), adaptive radiotherapy and image-guided radiotherapy.
  2. Translational research: application of biological knowledge of both cancer and healthy tissue in order to individualize treatment to the characteristics of each patient, each individual tumor.

Highlights 2015 / Radiation Oncology Group

  1. We achieved an increase in the number of patients treated with IMRT. In 2015 we treated 418 patients with IMRT, representing a 28% increase.
  2. The Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE) project was initiated in 2013. At present we have included 26 patients
  3. We initiated a dose escalation program using Image Guided RadioTherapy (IGRT) with fiducials, and have since treated 21 patients.
  4. Our group has set up a stereotaxic extracranial RT in lung cancer program and we have treated 4 patients.

PI Paper Pick /Radiation Oncology Group

Giralt J, Trigo J, Nuyts S, Ozsahin M, Skladowski K, Hatoum G, Daisne JF, Yunes Ancona AC, Cmelak A, Mesía R, Zhang A, Oliner KS, VanderWalde A. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015;16(2):221-232.

Mesía R, Henke M, Fortin A, Minn H, Yunes Ancona AC, Cmelak A, Markowitz AB, Hotte SJ, Singh S, Chan AT, Merlano MC, Skladowski K, Zhang A, Oliner KS, VanderWalde A, Giralt J. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015;16(2):208-220.

Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo

FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localized prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16(3):320-327.

Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016;34(12):1300-1308. Epub 2015 Dec 28.

Horizons 2016 /Radiation Oncology Group

  1. Continue to implement IMRT with VMAT.
  2. Develop an estereotactic extracranial radiotherapy program in liver and oligometastases.
  3. Implement breast cancer techniques including partial breast irradiation and prone position.
  4. Achieve ISO 9001/2008 accreditation in the field of radiotherapy.
  5. Identify factors associated with clinical response in advanced head and neck tumors treated with radiotherapy and cetuximab.

Publications / Radiation Oncology Group

  1. Mesía R, Henke M, Fortin A, Minn H, Yunes Ancona AC, Cmelak A, Markowitz AB, Hotte SJ, Singh S, Chan AT, Merlano MC, Skladowski K, Zhang A, Oliner KS, VanderWalde A, Giralt J. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):208-20.
  2. Alsina M, Landolfi S, Aura C, Caci K, Jimenez J, Prudkin L, Castro S, Moreno D, Navalpotro B, Tabernero J, Scaltriti M. Cyclin E amplification/overexpression is associated with poor prognosis in gastric cancer. Ann Oncol. 2015 Feb;26(2):438-9.
  3. Sclafani F, Peckitt C, Cunningham D, Tait D, Giralt J, Glimelius B, Keränen SR, Bateman A, Hickish T, Tabernero J, Thomas J, Brown G, Oates J, Chau I. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):303-12.
  4. Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martinez-Ricarte F, Rodon J, Auger C, Salas-Puig J, Santamarina E, Martinez-Saez E. Prognostic implications of epilepsy in glioblastomas. Clin Neurol Neurosurg. 2015 Oct 17;139:166-171.
  5. Barro V, Velez R, Pacha D, Giralt J, Roca I, Aguirre M. Bernese Periacetabular Osteotomy in a Hip Extra-Articular Resection Followed by Reconstruction Using an Extracorporeal Irradiated Acetabulum Autograft with Megaprosthesis, for Proximal Femur Osteosarcoma in a Pediatric Patient. Case Rep Med. 2015;2015:813683.
  6. López Torrecilla J, Hervás A, Zapatero A, Gómez Caamaño A, Macías V, HerruzoI, Maldonado X, Gómez Iturriaga A, Casas F, González San Segundo C. Uroncor consensus statement: Management of biochemical recurrence after radical radiotherapy for prostate cancer: From biochemical failure to castration resistance. Rep Pract Oncol Radiother. 2015 Jul-Aug;20(4):259-72.
  7. Morote J, Maldonado X, Morales-Bárrera R; en nombre del grupo multidisciplinario para el estudio y tratamiento del cáncer de próstata Vall d’Hebron. [Prostate cancer.]. Med Clin (Barc). 2015 Feb 26.
  8. Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localized prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7.
  9. Garcia Del Muro X, de Alava E, Artigas V, Bague S, Braña A, Cubedo R, Cruz J, Mulet-Margalef N, Narvaez JA, Martinez Tirado O, Valverde C, Verges R, Viñals J, Martin-Broto J. Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS). Cancer Chemother Pharmacol. 2015 Nov 12.
  10. Serrano C, Romagosa C, Hernández-Losa J, Simonetti S, Valverde C, Moliné T, Somoza R, Pérez M, Vélez R, Vergés R, Domínguez R, Carles J, Ramón Y Cajal S. RAS/MAPK pathway hyperactivation determines poor prognosis in undifferentiated pleomorphic sarcomas. Cancer. 2015 Oct 19.
  11. Zapatero A, González San Segundo C, Boladeras A, Gómez Caamaño A, LópezTorrecilla J, Maldonado X. Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies. Clin Transl Oncol. 2015 Mar;17(3):223-9.
  12. Giralt J, Trigo J, Nuyts S, Ozsahin M, Skladowski K, Hatoum G, Daisne JF, Yunes Ancona AC, Cmelak A, Mesía R, Zhang A, Oliner KS, VanderWalde A. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):221-32.2015 Jan 15.
  13. Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2015 Dec 28.
  14. Gómez Caamaño A, Zapatero A, López Torrecilla J, Maldonado X. Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain. Clin Transl Oncol. 2015 Nov 30.

Projects / Radiation Oncology Group

Funded Projects

  1. Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE)
    Supported through a European grant of the EU7th framework programme (FP7), this project aims at optimising 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.
  2. Radiogenomics 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.
  3. Molecular factors relevant for cetuximab effect: integration with radiation therapy in head and neck cancer (FIS)
    The aim of this study is to identify factors associated with clinical response in advanced head and neck tumors treated with cetuximab-radiotherapy in order to better select patients with greater chance of response to this treatment.
  1. 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.

Non Funded Projects

  1. Impact of natomical changes during the treatment with RT on the Distribution of dose in cancer patients with locally advanced Head and Neck cancer
  2. Radiofrequency ablation lumpectomy margins to reduce second surgery and improve local control in patients with breast cancer
  3. Breast irradiation, comparisons and analysis of dose distribution and reproducibility
  4. Phase II clinical Essay extracranial stereotactic radiotherapy in the treatment of locally advanced prostate cancer
  5. Instrumentation radiotherapy of the spine and paraspinal tumors and metastases
  6. Extracranial stereotactic radiotherapy in lung cancer, commissioning and validation of the technique
  7. Techniques for reducing toxicity: radiotherapy treatment in the pediatric patients with brain tumors
  8. Radiation treatment planning of gynecological tumors. Monitoring compliance in filling the urinary bladder
  9. Total marrow irradiation program for bone marrow transplantation in patients with multiple myeloma; dosimetric studys

Thoracic Tumors & Head and Neck Cancer Group / Enriqueta Felip

Imagen

Principal Investigator
Enriqueta Felip

Medical Oncologists
Neus Basté
Irene Braña
Susana Cedrés
Álex Martínez
Alejandro Navarro
Nuria Pardo

Summary / Thoracic Tumors & Head and Neck Cancer Group

The main focus of the Thoracic Tumors & Head and Neck Cancer Group is to tackle various aspects of lung cancer, the most frequently diagnosed tumor to date. Our group concentrates on a number of areas ranging from disease prevention, early detection, more accurate techniques in diagnosis and staging to advancing precision medicine and treatment of lung cancer. We are also highly dedicated to our program which focuses on targeted therapies in patients with specific molecular alterations and immunotherapy strategies.

In lung cancer patients with early-stage disease, we collaborate closely with thoracic surgeons and radiation therapists to better optimize the different treatment approaches and modalities set within a truly multidisciplinary setting. Since lung cancer patients sometimes suffer from severe symptoms associated with the disease, we strive to ameliorate them by working closely with a number of professionals from other disciplines. In patients with advancedstage disease, personalized therapy is now the standard approach and our key objective is the early implementation of molecular determinants to better select treatment options tailored to individual patients. Immunotherapy strategies have a role in the lung cancer management treatment algorithm; a number of protocols using this strategy are now ongoing in our unit.

We actively contribute to VHIO’s efforts aimed at early clinical drug development, and also deal with other less common thoracic malignancies such as small-cell lung cancer, mesothelioma, thymoma, and neuroendocrine tumors.

Strategic Goals / Thoracic Tumors & Head and Neck Cancer Group

  1. Contribute to early drug development and matched therapies for thoracic & head and neck tumors.
  2. Advance personalized medicine for lung cancer patients through translational research.
  3. Optimize novel treatment approaches (immunotherapy) for the management of patients with thoracic & head and neck malignancies.
  4. Further strengthen multidisciplinarity to provide optimal care for our patients.

Highlights 2015 / Thoracic Tumors & Head and Neck Cancer Group

  1. 500 new lung cancer patients including 20 cases of mesothelioma and 5 of thymoma.
  2. We continue to foster close multidisciplinary collaboration through our established lung cancer tumors committee which convenes twice a week.
  3. Implementation of pharmacogenomic approaches in advanced NSCLC 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.
  4. Our group has collaborated in the development of a number of drugs in lung cancer patients selected according to specific molecular alterations; some of which have already been approved by FDA and EMA as result of these studies.
  5. Identification of mechanisms of resistance to innovative targeted therapies; we have collaborated in the identification of C797S as a mechanism of acquired resistance to osimertinib.
  6. Active development of immunotherapy strategies in lung cancer patients.

PI Paper Pick / Thoracic Tumors & Head and Neck Cancer Group

Jänne PA; Yang JC; Kim DW; Planchard D;Ohe Y; Ramalingam SS; Ahn MJ; Kim SW; Su WC; Horn L; Haggstrom D; Felip E; Kim JH; Frewer P; Cantarini M; Brown KH; Dickinson PA; Ghiorghiu S; Ranson M. AZD9291 in EGFR Inhibitor-Resistant Non-Small-Cell Lung Cancer. N Engl J Med. 2015;372(18):1689-1699.

Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015;16(8):897-907.

Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D, Matthews SE, Cantarini M, Barrett JC, Jänne PA, Oxnard GR. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015;21(6):560-562.

Felip E, Concha Á, de Castro J, Gómez-Roman J, Garrido P, Ramírez J, Isla D, Sanz J, Paz-Ares L, López-Ríos F. Biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. 2015. Clin Transl Oncol. 2015;17(2):103-112.

Horizons 2016 / Thoracic Tumors & Head and Neck Cancer Group

  1. Potentiate and expand our translational research.
  2. Consolidate a basic research program in thoracic malignancies.
  3. Increase specific programs and activities focusing on other thoracic tumors (e.g. mesotheliomas, thymic carcinomas).

Publications / Thoracic Tumors & Head and Neck Cancer Group

  1. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015 Dec 18. pii: S0140-6736(15)01281-7. doi: 10.1016/S0140-6736(15)01281-7. [Epub ahead of print] PubMed PMID: 26712084.
  2. Karachaliou N, Codony-Servat J, Teixidó C, Pilotto S, Drozdowskyj A, Codony-Servat C, Giménez-Capitán A, Molina-Vila MA, Bertrán-Alamillo J, Gervais R, Massuti B, Morán T, Majem M, Felip E, Carcereny E, García-Campelo R, Viteri S, González-Cao M, Morales-Espinosa D, Verlicchi A, Crisetti E, Chaib I, Santarpia M, Luis Ramírez J, Bosch-Barrera J, Felipe Cardona A, de Marinis F, López-Vivanco G, Miguel Sánchez J, Vergnenegre A, Sánchez Hernández JJ, Sperduti I, Bria E, Rosell R. BIM and mTOR expression levels predict outcome to erlotinib in EGFR-mutant non-small-cell lung cancer. Sci Rep. 2015 Dec 7;5:17499. doi: 10.1038/srep17499. PubMed PMID: 26639561; PubMed Central PMCID: PMC4671004.
  3. De Mattos-Arruda L, Mayor R, Ng CK, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015 Nov 10;6:8839. doi: 10.1038/ncomms9839. PubMed PMID: 26554728.
  4. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27. PubMed PMID: 26412456.
  5. Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, Garcia-Gomez R, Massuti B, Sánchez JM, Porta R, Ponce-Aix S, Moran T, Carcereny E, Felip E, Bover I, Insa A, Reguart N, Isla D, Vergnenegre A, de Marinis F, Gervais R, Corre R, Paz-Ares L, Morales-Espinosa D, Viteri S, Drozdowskyj A, Jordana-Ariza N, Ramirez-Serrano JL, Molina-Vila MA, Rosell R; Spanish Lung Cancer Group. Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial. JAMA Oncol. 2015 May;1(2):149-57. doi: 10.1001/jamaoncol.2014.257. PubMed PMID: 26181014.
  6. Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. doi: 10.1016/S1470-2045(15)00006-6. Epub 2015 Jul 5. PubMed PMID: 26156651.
  7. Vansteenkiste JF, Canon JL, Braud FD, Grossi F, De Pas T, Gray JE, Su WC, Felip E, Yoshioka H, Gridelli C, Dy GK, Thongprasert S, Reck M, Aimone P, Vidam GA, Roussou P, Wang YA, Di Tomaso E, Soria JC. Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study. J Thorac Oncol. 2015 Sep;10(9):1319-27. doi: 10.1097/JTO.0000000000000607. PubMed PMID: 26098748; PubMed Central PMCID: PMC4646607.
  8. Ramalingam S, Goss G, Rosell R, Schmid-Bindert G, Zaric B, Andric Z, Bondarenko I, Komov D, Ceric T, Khuri F, Samarzija M, Felip E, Ciuleanu T, Hirsh V, Wehler T, Spicer J, Salgia R, Shapiro G, Sheldon E, Teofilovici F, Vukovic V, Fennell D. A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1). Ann Oncol. 2015 Aug;26(8):1741-8. doi: 10.1093/annonc/mdv220. Epub 2015 May 21. PubMed PMID: 25997818.
  9. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D, Matthews SE, Cantarini M, Barrett JC, Jänne PA, Oxnard GR. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015 Jun;21(6):560-2. doi: 10.1038/nm.3854. Epub 2015 May 4. PubMed PMID: 25939061; PubMed Central PMCID: PMC4771182.
  10. Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817. PubMed PMID: 25923549.
  11. Eberhardt WE, De Ruysscher D, Weder W, Le Péchoux C, De Leyn P, Hoffmann H, Westeel V, Stahel R, Felip E, Peters S; Panel Members. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol. 2015 Aug;26(8):1573-88. doi: 10.1093/annonc/mdv187. Epub 2015 Apr 20. PubMed PMID: 25897013.
  12. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. doi: 10.1056/NEJMoa1501824. Epub 2015 Apr 19. PubMed PMID: 25891174.
  13. Gridelli C, Balducci L, Ciardiello F, Di Maio M, Felip E, Langer C, Lilenbaum RC, Perrone F, Senan S, de Marinis F. Treatment of Elderly Patients With Non-Small-Cell Lung Cancer: Results of an International Expert Panel Meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2015 Sep;16(5):325-33. doi: 10.1016/j.cllc.2015.02.006. Epub 2015 Mar 7. Review. PubMed PMID: 25862554.
  14. Cedrés S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, Martinez-Marti A, Martinez P, Felip E. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015 Mar 16;10(3):e0121071. doi: 10.1371/journal.pone.0121071. eCollection 2015. PubMed PMID: 25774992; PubMed Central PMCID: PMC4361537.
  15. Cappuzzo F, Moro-Sibilot D, Gautschi O, Boleti E, Felip E, Groen HJ, Germonpré P, Meldgaard P, Arriola E, Steele N, Fox J, Schnell P, Engelsberg A, Wolf J. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus. Lung Cancer. 2015 Feb;87(2):89-95. doi: 10.1016/j.lungcan.2014.12.010. Epub 2014 Dec 18. Review. PubMed PMID: 25576294.
  16. Felip E, Concha Á, de Castro J, Gómez-Román J, Garrido P, Ramírez J, Isla D, Sanz J, Paz-Ares L, López-Ríos F. Biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol. 2015 Feb;17(2):103-12. doi: 10.1007/s12094-014-1248-9. Epub 2014 Oct 29. Review. PubMed PMID: 25351175.
  17. Heigener DF, Pereira JR, Felip E, Mazal J, Manzyuk L, Tan EH, Merimsky O, Sarholz B, Esser R, Gatzemeier U. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial. Target Oncol. 2015 Jun;10(2):255-65. doi: 10.1007/s11523-014-0336-7. Epub 2014 Sep 9. PubMed PMID: 25195590.

Projects / Thoracic Tumors & Head and Neck Cancer Group

  1. An Epidemiological Study of ALK Gene Rearrangement: Prevalence and Clinical Outcomes in Patients with Non-Small Cell Lung Cancer in Europe
  2. Tecnologías moleculares de última generación para el estudio y abordaje terapéutico de los tipos de cáncer
  3. Inhibidores de la Ruta Wnt/Beta-Catenin como prometedora terapia para el tratamiento del cáncer de pulmón
  1. Research collaboration: ETOP-VHIO Lungscape 2
  2. Research collaboration: ETOP-VHIO Lungscape 3
  3. Detección de la mutación T790M mediante tecnología BEAMing en pacientes con CPNP y EGFR mutado en estadio IV