PROGRAMS & GROUPS

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JOAN SEOANE

Translational Research Program Director
"At VHIO we aim to deliver on the promise of precision oncology by translating discovery into more effective treatments for patients as quickly as possible."

Click here to read our Program Director´s synopsis 2015

VHIO’s Translational Research Program is dedicated to improving and accelerating the integration of preclinical and clinical research. We consequently strive to translate advances in molecular research into benefits at patient level as swiftly as possible by both tackling the disease from all angles and generating synergies between molecular and clinical cancer research.

One of the main challenges we face in our collective battle to conquer cancer is tumor diversity. Cancer is an extremely complex, heterogeneous, and fluctuating disease given that tumors are molecularly diverse and evolve over time. Moreover, tumors are formed by cells with multifarious states of proliferation, differentiation, motility, and, importantly, varying sensitivity to treatment. In short, each patient has a unique tumor with a particular combination of genomic aberrations that can change during tumor progression. Patients should therefore be treated with the optimal compound/combination of therapies to respond to the specificities of their respective disease. Since the selection of the most appropriate treatment depends on the specific molecular taxonomy of the tumor in a given time, the challenge is to identify which treatment should be linked to which patient and in so doing, further advance precision medicine in oncology.

In order to improve anti-cancer therapies through the combination of compounds targeting all cell types within a tumor, we must better understand the nature of intratumoral heterogeneity. Among the different cell types forming intratumoral heterogeneity, some cells with stem cell characteristics have been identified. Known as Cancer-Initiating Cells (CICs) or Cancer Stem Cells (CSCs), these cells are characterized by their self-renewing capacity, multi-lineage differentiation properties, high oncogenic potential, and ability to replicate the heterogeneity of original human tumors in mouse models. CICs are also considered responsible for the initiation, recurrence and chemo- and radio-resistance of tumors indicating that more effective therapies will be identified via strategies aimed at targeting the stem-cell-like component of tumors. Few pharmacological compounds have yet been shown to successfully do so.

In order to explore the two levels of cancer heterogeneity, we investigate cancer as faithfully as possible to that of a real tumor and generate patient-derived models both in vitro and in vivo. Tumor specimens are obtained shortly upon surgical resection and we study tumor cells as well as cancer stem cells. The next step is to generate mouse models reproducing the characteristics of the tumor from the patient. Both VHIO’s Stem Cells & Cancer Group led by Héctor G. Palmer, and my own Gene Expression & Cancer Group have developed these models for brain and colon cancer respectively, work which has led to important findings published in top-tier journals.

Providing optimal treatment tailored to individual patients relies on team work, studying cancer as closely as possible to the real patient, and tackling cancer heterogeneity head-on. VHIO’s Translational Research Program is committed to delivering on this promise by catalyzing the transfer of new insight generated by scientific research into the true benefit for patients.

TRANSLATIONAL RESEARCH GROUPS

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Gene Expression & Cancer
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Joan Seoane
Principal Investigator
Stem Cells & Cancer
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Héctor G. Palmer
Principal Investigator

Gene Expression & Cancer Group / Joan Seoane

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Principal Investigator
Joan Seoane

Medical Oncologists
Leticia de Mattos
Davis Torrejón Castro

Post-Doctoral Fellows
Vanessa Chiganças
Isabel Huber
Regina Mayor
Josep Lluís Parra-Palau
Atenea Soto

Graduate Students
Ester Arroba
Gerard Folch
Ada Sala

Technicians
Alexandra Arias
Isabel Cuartas
Rosa Gil
Carolina Raventós
Cristina Sánchez

Summary / Gene Expression & Cancer Group

Our group focuses on the study of brain tumors - primary tumors and brain metastasis. These are some of the most aggressive cancers and advancing progress within this field is consequently critical.

One of the most important challenges in cancer is the heterogeneity of tumors, which we are studying at both the level of genomic alterations and that of cell differentiation state.

Tumors are composed by a mosaic of cell subclones that differ in their genomic alterations. We are studying genomic diversity present in glioblastoma and how intratumor genomic heterogeneity evolves over time in response to treatment. Following Darwinian selection rules, the cellular subclones enriched in response to treatment are those that will confer resistance to treatment and facilitate the identification of novel therapeutic targets to counter tumor resistance and relapse.

Besides the genomic intratumor diversity, cells within tumors although having the same genomic alterations might present differences in the epigenomic state. In particular, we are analyzing a subpopulation of undifferentiated cells responsible for tumor initiation and relapse. These cells have stem cell-like characteristics and are known as cancer-initiating cells (CICs) or cancer stem cells. CICs are considered to be responsible for the initiation, recurrence and chemo- and radio-resistance of tumors and therefore represent crucial therapeutic targets. Advancing our understanding of the molecular mechanisms involved in these cells is consequently paramount. We aim to identify novel markers for CICs, obtain new insights into the signaling pathways and molecular mechanisms involved in CICs, and design novel therapeutic approaches to target them.

Finally, due to genomic intratumor heterogeneity, we are interested in developing non-invasive methods to assess the genomic alterations present in tumors. We are studying cell-free circulating tumor DNA in fluids from patients with brain tumors. Tumors shed DNA into the blood stream and the subsequent sequencing of the circulating DNA enables the accurate, noninvasive molecular characterization of tumors. These circulating markers facilitate the diagnosis, monitoring and identification of actionable gene mutations of tumors.

Strategic Goals / Gene Expression & Cancer Group

  1. Identify both new therapeutic targets against brain tumors as well as novel biomarkers to predict response to therapy.
  2. Study intratumor heterogeneity.
  3. Achieve a better understanding of the molecular mechanisms implicated in cancer initiating cells/cancer stem cells.
  4. Develop methods for non-invasive molecular diagnosis through the study of circulating biomarkers.
  5. Generate patient-derived mouse models of brain tumors.

Highlights 2015 / Gene Expression & Cancer Group

  1. Our efforts have led to several publications in 2015. Specifically, we would like to highlight the publication De Mattos Arruda et al. Nature Communications 2015. Liquid biopsy in plasma has already proven useful across several tumor types but not, until now, in brain tumors. Our group has discovered cerebrospinal fluid to be highly enriched in circulating tumor DNA -- enabling the characterization of brain tumors. Cerebrospinal fluid flows through the brain parenchyma and the spinal cord and can be sampled via lumbar puncture. Cerebrospinal fluid liquid biopsy is a less invasive approach promising a novel, pioneering line of research into biomarkers that will both enable the crucial tracking of disease as well as ultimately help to evaluate and monitor drug efficacy as the cancer progresses
  2. Joan Seoane received the prestigious Doctores Diz- Pintado National Prize.

PI Paper Pick / Gene Expression & Cancer Group

De Mattos-Arruda L, Mayor R, Ng CKY, 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.

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 2nd, 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. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015;5(11):1164-1177.

Iyengar PV, Jaynes P, Rodon L, Lama D, Law KP, Lim YP, Verma C, Seoane J, Eichhorn PJ. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Sci Rep. 2015;5:14733.

Rodon J, Carducci MA, Sepulveda-Sanchez JM, Azaro A, Calvo E, Seoane J, Brana I, Sicart E, Gueorguieva I, Cleverly AL, Sokalingum Pillay N, Desaiah D, Estrem ST, Paz-Ares L, Holdoff 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.

Horizons 2016 / Gene Expression & Cancer Group

  1. Identify novel therapeutic targets against glioblastoma.
  2. Establish novel markers of response to therapy in order to better patient stratification in clinical trials.
  3. Develop improved methods for non-invasive molecular diagnosis.

Publications / Experimental Therapeutics Group

  1. De Mattos-Arruda L, Mayor R, Ng CKY, 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. Nature Communications. 2015;6:8839.
  2. 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. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015;6(35):37269-80.
  3. 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 2nd, 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. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015;5(11):1164-77.
  4. Iyengar PV, Jaynes P, Rodon L, Lama D, Law KP, Lim YP, Verma C, Seoane J, Eichhorn PJ. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Sci Rep. 2015;5:14733.
  5. Ulloa F, Gonzàlez-Juncà A, Meffre D, Barrecheguren PJ, Martínez-Mármol R, Pazos I, Olivé N, Cotrufo T, Seoane J, Soriano E. Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth. PLoS One. 2015;10(3):e0119707.
  6. Rodon J, Carducci MA, Sepulveda-Sanchez JM, Azaro A, Calvo E, Seoane J, Brana I, Sicart E, Gueorguieva I, Cleverly AL, Sokalingum Pillay N, Desaiah D, Estrem ST, Paz-Ares L, Holdoff 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. 2015;21(3):553-60.
  7. Rodon 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;33(2):357-70.

Projects / Gene Expression & Cancer Group

Grants:

  1. Grantor: European Research Council (ERC) Proof of Concept Grant
    Title: Development of a more effective and safer therapeutic antibody for cancer treatment with a dual mechanism of action to eliminate CSCs and reactivate the tumour's immune system.
    CSC-IS. Project reference: 665671
    Role in the project: Principal Investigator
    2015-2016
  2. Grantor: MINECO-RETOS
    Title: Desarrollo de un fármaco innovador y personalizado para el tratamiento del cáncer que reactiva el sistema inmune contra el tumor y elimina las células madre tumorales.
    Role in the project: Principal Investigator
    2015-2018

Participation in Research Contracts:

  1. Preclinical evaluation of MOSAIC's MSC-1 antibody
    MOSAIC BIOMEDICALS, S.L.
    2015-2016
    Principal Investigator: Joan Seoane

Awards / Gene Expression & Cancer Group

Grantor: Fundación para la Investigación del Cáncer de la Universidad de Salamanca (FICUS) y el Centro de Investigación del Cáncer (CIC).
IV Premio Nacional Doctores Diz Pintado. January 2015.

Stem Cells & Cancer Group / Héctor G. Palmer

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Principal Investigator
Héctor G. Palmer

Post-Doctoral Fellows
Oriol Arqués
Jordi Martínez-Quintanilla
Isabel Puig
Stephan Tenbaum

Technicians
Irene Chicote
Génesis Martín
Lorena Ramírez

Summary / Stem Cells & Cancer Group

Our main interest is to better understand the molecular mechanisms that confer tumors the ability to self-renew, resist therapy, relapse and metastasize – all definitive factors in the survival of patients.

We are dedicated to studying the consequences of intratumoral cell heterogeneity for tumor evolution and patient survival. Among the different cell populations that build an heterogeneous tumor, Cancer Stem Cells (CSC) are at the apex of a differentiation process within the cancerous tissue -- somewhat reminiscent of the hierarchy present in the normal tissue from which they originate. CSC can also compose the small reservoir of drug-resistant cells that are responsible for relapse after chemotherapy-induced remission, or give rise to distant metastasis. It is therefore becoming evident that therapies failing to eliminate cancer stem cells may allow re-growth of the tumor.

Colorectal cancer is our prime focus of study. At molecular level, we are analyzing the role of those oncogenic pathways that control the fate of Colon Cancer Stem Cells (CoCSC). RAS/PI3K/AKT and Wnt/beta-catenin pathways are two drivers of cancer stem cell fate and lead to progression across many tumor types.

Over recent years we have described a novel mechanism of resistance to PI3K and AKT inhibitory drugs conferred by beta-catenin in colorectal cancer. This is of great clinical relevance since many patients in clinical trials are not responding to these drugs and no molecular explanation behind resistance had previously been evidenced. These findings will facilitate the selection of ‘sensitive’ patients based on their expression of particular biomarkers predicting drug-response.

We are currently focusing on a new generation of Wnt/betacatenin inhibitory drugs in close collaboration with several major pharmaceutical companies and have already produced experimental evidence on the efficacy and mechanisms of action of these drugs in pre-clinical models of colorectal cancer with patient-derived xenografts. This marks an important milestone in the field – for decades colorectal cancer was described as a paradigmatic tumor addicted to the oncogenic Wnt/beta-catenin pathway. We also work on identifying the molecular determinants of response to these drugs that could become robust biomarkers to select ‘sensitive’ patients and guide the design of future clinical trials. Some of these predictive biomarkers are mutations affecting components of the Wnt/beta-catenin pathway, whose identification can be perfectly standardized in clinical practice for patient selection.

Our collaboration with the Medical Oncology Service at the Vall d’Hebron University Hospital and pharmaceutical companies will accelerate the translation of our findings into clinical practice and hopefully revert the long-stalled scenario of CRC therapies.

Our group has developed a collection of patient-derived xenograft (PDX) models from more than 100 CRC patients. They are derived from primary tumors or liver metastasis. More recently we have also generated around 30 clinical trial associated xenografts (CTAX) from patients enrolled in clinical studies. All these models faithfully recapitulate original patient tumors and, most importantly, their response to treatments, becoming the gold standard for studying mechanisms of drug-resistance or sensitivity.

Strategic Goals /Stem Cells & Cancer Group

  1. Describe key molecular mechanisms that confer CoCSC their capacity to self-renew and resist conventional or target directed therapies.
  2. Unmask molecular drivers of CSC quiescence, clinical relevance in cancer progression and evaluate their potential inhibition to eradicate CoCSC.
  3. Study the efficacy and mechanism of action of new Wnt/ beta-catenin inhibitory drugs for the treatment of CRC.
  4. Identify the genetic determinants of sensitivity or resistance to the novel generation of Wnt/beta-catenin inhibitors.
  5. Implement predictive biomarkers of response to therapeutic Wnt/beta-catenin inhibitors and other targeted therapies.
  6. Expand our collection of PDX models and start working on PDX models derived from other tumor types such as lung cancer.

Highlights 2015 / Stem Cells & Cancer Group

  1. We have established a network to derive tumour cells from CRC patients directly post surgery. This has involved careful and committed coordination since it involves the time and cooperation between a team comprised of an oncologist, pathologist, surgeons and our group members. This network has resulted in successfully derived PDX models from more than 100 CRC patients (primary and liver metastasis) and is currently expanding to include more professionals, tumor types and small biopsies of patients in clinical trials. The growing collection of PDXs includes all pathological, clinical, genetic and biological data for each CRC patient. Based on this multidisciplinary approach our group has been able to develop different research projects with robust and rapid translation to cancer patients.
  2. One first example of such a project started at the end of 2008, investigating the role of beta-catenin and FOXO3a transcription factors in CRC. Initially a modest project, it resulted in a Nature Medicine publication in 2012 (Tenbaum et al. Nat Med. 2012). We described the capacity of nuclear beta-catenin to promote metastasis in coordination with FOXO3a and to confer resistance to PI3K and AKT inhibitory drugs. These findings have become relevant to understand the enhanced resistance of CRC patients to this family of drugs. Indeed, many cancer patients are being treated with these inhibitors in phase I clinical trials worldwide and negative results on response could not be explained prior to our publication. Our findings have had a significant impact on basic and clinical research, being cited and reviewed in major journals (Nature Reviews Molecular Cell Biology 2013 Feb;14(2):83-97. Nature Reviews Drug Discovery 2012 Dec;11(12):923-36. Nature Medicine, New & Views.18, 854–856 (2012); Cancer Discovery July 2012 2:579; World J Biol Chem 2012 September 26; 3(9): 175-179).
  3. Our discovery also attracted the interest of major pharmaceutical companies (Novartis, Merk Serono, AstraZeneca and Vernalis). They are currently interested in two distinctive traits of our group: our clinically and genetically annotated PDXs collection of CRC tumours and our knowledge on oncogenic signalling and basic cancer research. Pharmaceutical companies are at the same time providing financial support and high scientific and quality standards for collaborative projects.
  4. The project with Novartis has facilitated the study of the efficacy of a new Wnt/beta-catenin inhibitor that breaks the innate resistance of CRC tumours to PI3K or AKT inhibitory drugs. We have also identified possible mechanisms and markers that would predict sensitivity of CRC patients to therapeutic Wnt/beta-catenin inhibitors. The data generated include results with PDX models and clinical trials with CRC patients. These findings could well mark a milestone for CRC therapeutics since this is classically a Wnt/beta-catenin addicted tumour type for which treatments have not improved for the last 8 years.
  5. In parallel to this major project, we also completed a study on SPRY2, defining its relevance in CRC and its regulation as a FOXO3a and beta-catenin target gene. The results from these experiments initiated by Paloma Ordoñez were published in Oncogene (Ordoñez P, et al. 2013).
  6. Our team also defined the protocols to derive cells from patients and to generate an orthotopic model of CRC by injecting them in the cecum wall of immunodeficient mice. Such a model recapitulates the main features of the advanced disease, generating metastasis in liver and lung, carcinomatoses and invasion of local and distant lymph nodes. Metastasis was followed by live imaging using radioactive glucose (18FDG) and Positron Emission Tomography (PET) in collaboration with the group headed by S. Rojas at the Institute of High Technology (IAT). This work was published in Clinical Cancer Research (Puig I, et al. 2013).
  7. Since 2009, work developed by I. Puig has also allowed us to characterize the molecular determinants of a distinct population of slow cycling cancer stem cells within CRC tumours. The results obtained indicate that this small population of cells is chemoresistant and retains an enhanced cancer initiation potential based on the distinctive activity of particular epigenetic enzymes.
  8. In collaboration with the laboratory of D. Bonnet at Cancer Research UK, we have also described the molecular traits that define a new population of human quiescent haematopoietic stem cells that present a repressive Wnt phenotype among many other distinctive features (Anjos-Afonso F, et al. Cell Stem Cell. 2013).

PI Paper Pick / Experimental Therapeutics Group

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. Tankyrase inhibition blocks Wnt/b-catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Clin Cancer Res. 2016;22(3):644-656. Epub 2015 Jul 29.

García-García C; Rivas M; Ibrahim Y; Calvo MT; Grueso J; Antón P; Aura C; Jessen K; Dienstmann R; Palmer HG; Tabernero J; Scaltriti M; Baselga J; Serra V. Sensitivity to MEK and mTORC1/2 inhibition in colorectal cancer is dictated by TP53 mutational status. Clin Cancer Res. 2015;21(24):5499-5510.

Barbáchano A; Pereira F; Segura M; Ordoñez-Morán P; González-Sancho JM; Fernández-Barral A; Hanniford D; Martínez N; Real FX; Palmer HG; Rojas JM; Hernando E; Muñoz A. SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150. Oncogene. 2015;5:14733. Epub 2015 Oct 12.

Herrero A, Pinto A, Colón-Bolea P, Casar B, Jones M, Agudo-Ibáñez L, Vidal R, Tenbaum SP, Nuciforo P, Valdizán EM, Horvath Z, Orfi L, Pineda-Lucena A, Bony E, Keri G, Rivas G, Pazos A, Gozalbes R, Palmer HG, Hurlstone A, Crespo P. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell. 2015;28(2):170-182.

Horizons 2016 / Experimental Therapeutics Group

  1. Evaluate the relevance of those key factors that control the link between stemness and quiescence in CoCSC.
  2. Test the efficacy of target-therapies to eliminate slow cycling (quiescent) CoCSC.
  3. To reveal and validate the clinical potential of new biomarkers to identify slow cycling CoCSC in CRC patients.
  4. We will also study the efficacy of new Wnt/beta-catenin inhibitory drugs in colon cancer and identify new biomarkers to select patients sensitive to this target-directed therapy.

Publications / Stem Cells & Cancer Group

  1. Aleix Prat, Barbara Adamo, Cheng Fan, Vicente Peg, Maria Vidal, Patricia Galván, Ana Vivancos, Paolo Nuciforo, Héctor G Palmer, Shaheenah Dawood, Jordi Rodon, Santiago Ramon y Cajal, Josep Maria Del Campo, Enriqueta Felip, Josep Tabernero, and Javier Cortés. Genomic Analyses across Six Cancer Types Identify Basal-like Breast Cancer as a Unique Molecular Entity. Scientific Reports. 2013 Dec 18;3:354.
  2. Isabel Puig, Irene Chicote, Stephan P. Tenbaum, Oriol Arqués, José Raúl Herance, Juan D. Gispert, José Jimenez, Stefania Landolfi, Karina Caci, Helena Allende, Leire Mendizabal, Debora Moreno, Ramón Charco, Eloy Espín, Aleix Prat, Maria Elena Elez, Guillem Argilés, Ana Vivancos, Josep Tabernero, Santiago Rojas, Palmer HG. A Personalized Pre-clinical Model to Evaluate the Metastatic Potential of Patient-derived Colon Cancer Cells. Clinical Cancer Research. 2013 Dec 15;19(24):6787-801.
  3. Anjos-Afonso F, Currie E, Palmer HG, Foster KE, Taussig DC, Bonnet D. CD34(-) Cells at the Apex of the Human Hematopoietic Stem Cell Hierarchy Have Distinctive Cellular and Molecular Signatures. Cell Stem Cell. 2013 Aug 1;13(2):161-74.
  4. Paloma Ordóñez-Morán, Anja Irmisch, Antonio Barbáchano, Stephan Tenbaum, Irene Chicote, Stefania Landolfi, Josep Tabernero, Joerg Huelsken, Alberto Muñoz, Palmer HG. SPROUTY2 is a beta-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer. Oncogene. 2013 Apr 29. doi: 10.1038/onc.2013.140.

Projects / Stem Cells & Cancer Group

  1. New drugs to target the oncogenic Wnt/beta-catenin pathway (CIBOT)
    Novartis International AG
    2013-2016
    Principal Investigator: Héctor G. Palmer
  2. Wnt/beta-catenin inhibitors to treat colorectal cancer
    Merck Serono GmbH
    2013-2016
    Principal Investigator: Héctor G. Palmer
  3. Defining clinically actionable genetic alterations in DNA repair with in vivo response to the PARP inhibitor Olaparib
    Astrazeneca
    2014-2016
    Principal Investigators: Héctor G. Palmer, Joan Seoane and Violeta Serra
  1. Inhibición terapéutica de la ruta oncogénica Wnt/beta-cateninaen cáncer colorectal. PI14/00103
    Instituto de Salud Carlos III
    2015-2017
    Principal Investigator: Héctor G. Palmer
  2. Inhibición terapéutica de la ruta oncogénica Wnt/beta-catenina en cáncer colorectal
    Fundación de la Asociación Española Contra el Cáncer (AECC).
    2015-2018
    Principal Investigators: Stephan Tenbaum & Héctor G. Palmer
  3. Therapeutic inhibition of the oncogenic Wnt/beta-catenin pathway in mismatch repair deficient hypermutant tumors
    European Commission. MARIE SKŁODOWSKA-CURIE ACTIONS
    2016-2018
    Principal Investigators: Jordi Martínez & Héctor G. Palmer

Awards / Stem Cells & Cancer Group

FERO Foundation Fellowship: Personalized genetic studies to investigate drug-resistance and relapse in colon cancer - Unmasking hiding resistant clones.

Patents / Stem Cells & Cancer Group

Title: METHODS OF TREATING COLORECTAL CANCERS HARBORING UPSTREAM WNT PATHWAY MUTATIONS.
Patent Office: United States Patent and Trademark Office. Application Number: 62/119,939.
Patentee: Novartis AG
Profit entity: Novartis AG
Inventors: Linda BAGDASARIAN, Feng CONG, Savina JAEGER, Margaret Elise MCLAUGHLIN, Ronald MEYER, Andrea MYERS, Michael Ross PALMER, Youzhen WANG, Stephen David WOOLFENDEN, Ana VIVANCOS, Héctor PALMER .