Chemotherapy and predictive biomarkers Lab


​Eva Maritinez-Balibrea- Group Leader
Vicenç Ruiz de Porras - Postdoctoral researcher
Cristina Queralt - Postdoctoral researcher
Sara Bystrup - PhD Student
Sara Cabrero - PhD Student
Neus Cantariño - PhD Student
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Our group studies the molecular processes through which tumor cells develop resistance to chemotherapy in the treatment of patients with colorectal cancer (CRC) and works very closed to the team of oncologists at the ICO-HUGTiP. By identifying the factors responsible of this chemoresistance, we aim to contribute to the discovery of biomarkers that will improve the selection of effective treatments and to the development of new therapeutic strategies. To achieve these goals, we study cell models of acquired resistance and analyze gene or protein expression patterns as well as common genetic variants in genes that may be involved in the action of chemotherapy agents, using patient blood and/or tumor samples. The group's global objective is to optimize treatment to enhance prognosis and improve patients’ quality of life.
  • Martínez-Cardús A, Moran S, Musulen E, Moutinho C, Manzano JL, Martinez-Balibrea E, Tierno M, Élez E, Landolfi S, Lorden P, Arribas C, Müller F, Bock C, Tabernero J, Esteller M. Epigenetic Homogeneity Within Colorectal Tumors Predicts Shorter Relapse-free and Overall Survival Times for Patients With Loco-regional Cancer. Gastroenterology. 2016 Aug 10. pii: S0016-5085(16)34892-2. doi: 10.1053/j.gastro.2016.08.001. PMID: 27521480.

  • Gonçalves-Ribeiro S, Guillen Díaz-Maroto N, Berdiel-Acer M, Soriano A, Guardiola J, Martínez-Villacampa M, Salazar R, Capellà G, Villanueva A, Martínez-Balibrea E, Molleví DG. Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells. Oncotarget. 2016 Aug 8. doi: 10.18632/oncotarget.11121. PMID: 27517495.

  • Manzano JL, Layos L, Bugés C, de Los Llanos Gil M, Vila L, Martínez-Balibrea E, Martínez-Cardús A. Resistant mechanisms to BRAF inhibitors in melanoma.Ann Transl Med. 2016 Jun;4(12):237. doi: 10.21037/atm.2016.06.07. Review. PMID: 27429963; PMCID: PMC4930524.

  • Ruiz de Porras V, Bystrup S, Martínez-Cardús A, Pluvinet R, Sumoy L, Howells L, James MI, Iwuji C, Manzano JL, Layos L, Bugés C, Abad A, Martínez-Balibrea E. Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway. Sci Rep. 2016 Apr 19;6:24675. doi: 10.1038/srep24675. PMID: 27091625; PMCID: PMC4835769.

  • Martinez-Balibrea E, Martínez-Cardús A, Ginés A, Ruiz de Porras V, Moutinho C, Layos L, Manzano JL, Bugés C, Bystrup S, Esteller M, Abad A. Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance. Mol Cancer Ther. 2015 Aug;14(8):1767-76. doi: 10.1158/1535-7163.MCT-14-0636. Review. PMID: 26184483.

  • Ginés A, Bystrup S, Ruiz de Porras V, Guardia C, Musulén E, Martínez-Cardús A, Manzano JL, Layos L, Abad A, Martínez-Balibrea E. PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition in HT29 Human Colorectal Cancer Cell Lines. PLoS One. 2015 May 8;10(5):e0123830. doi: 10.1371/journal.pone.0123830. eCollection 2015. PMID: 25955657; PMCID: PMC4425499.
 
  • Mezquita B, Pineda E, Mezquita J, Mezquita P, Pau M, Codony-Servat J, Martínez-Balibrea E, Mora C, Maurel J, Mezquita C. LoVo colon cancer cells resistant to oxaliplatin overexpress c-MET and VEGFR-1 and respond to VEGF with dephosphorylation of c-MET. Mol Carcinog. 2016 May;55(5):411-9. doi: 10.1002/mc.22289. PMID: 25647613. IF: 4,722 Q1
 
  • Dias MM, Pignon JP, Karapetis CS, Boige V, Glimelius B, Kweekel DM, Lara PN, Laurent-Puig P, Martinez-Balibrea E, Páez D, Punt CJ, Redman MW, Toffoli G, Wadelius M, McKinnon RA, Sorich MJ. The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis. Pharmacogenomics J. 2014 Oct;14(5):424-31. doi: 10.1038/tpj.2014.16. PMID: 24709690.
 
  • Lopez-Serra P, Marcilla M, Villanueva A, Ramos-Fernandez A, Palau A, Leal L, Wahi JE, Setien-Baranda F, Szczesna K, Moutinho C, Martinez-Cardus A, Heyn H, Sandoval J, Puertas S, Vidal A, Sanjuan X, Martinez-Balibrea E, Viñals F, Perales JC, Bramsem JB, Ørntoft TF, Andersen CL, Tabernero J, McDermott U, Boxer MB, Vander Heiden MG, Albar JP, Esteller M. A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nat Commun. 2014 Apr 3;5:3608. doi: 10.1038/ncomms4608. PMID: 24699711; PMCID: PMC3988805.
 
  • Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, Wang H, Love S, Julier P, Scudder C, Nicholson G, Gonzalez-Neira A, Martin M, Sargent D, Green E, McLeod H, Zanger UM, Schwab M, Braun M, Seymour M, Thompson L, Lacas B, Boige V, Ribelles N, Afzal S, Enghusen H, Jensen SA, Etienne-Grimaldi MC, Milano G, Wadelius M, Glimelius B, Garmo H, Gusella M, Lecomte T, Laurent-Puig P, Martinez-Balibrea E, Sharma R, Garcia-Foncillas J, Kleibl Z, Morel A, Pignon JP, Midgley R, Kerr D, Tomlinson I. Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol. 2014 Apr 1;32(10):1031-9. doi: 10.1200/JCO.2013.51.1857. Review. PMID: 24590654; PMCID: PMC4879695.
 
  • Moutinho C, Martinez-Cardús A, Santos C, Navarro-Pérez V, Martínez-Balibrea E, Musulen E, Carmona FJ, Sartore-Bianchi A, Cassingena A, Siena S, Elez E, Tabernero J, Salazar R, Abad A, Esteller M. Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer. J Natl Cancer Inst. 2014 Jan;106(1):djt322. doi: 10.1093/jnci/djt322. PMID: 24273214; PMCID: PMC3906989.

  • Codony-Servat J, Garcia-Albeniz X, Pericay C, Alonso V, Escudero P, Fernández-Martos C, Gallego R, Martínez-Cardús A, Martinez-Balibrea E, Maurel J. Soluble FAS in the prediction of benefit from cetuximab and irinotecan for patients with advanced colorectal cancer. Med Oncol. 2013 Mar;30(1):428. doi: 10.1007/s12032-012-0428-0. Epub 2013 Jan 22. PMID: 23338968.

  • Yin M, Yan J, Martinez-Balibrea E, Graziano F, Lenz HJ, Kim HJ, Robert J, Im SA, Wang WS, Etienne-Grimaldi MC, Wei Q. ERCC1 and ERCC2 polymorphisms predict clinical outcomes of oxaliplatin-based chemotherapies in gastric and colorectal cancer: a systemic review and meta-analysis. Clin Cancer Res. 2011 Mar 15;17(6):1632-40. doi: 10.1158/1078-0432.CCR-10-2169. Review. PMID: 21278243; PMCID: PMC3060288.

  • Martinez-Balibrea E, Abad A, Martínez-Cardús A, Ginés A, Valladares M, Navarro M, Aranda E, Marcuello E, Benavides M, Massutí B, Carrato A, Layos L, Manzano JL, Moreno V. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy. Br J Cancer. 2010 Aug 10;103(4):581-9. doi: 10.1038/sj.bjc.6605776. PMID: 20628391; PMCID: PMC2939780.

  • Martinez-Balibrea E, Plasencia C, Ginés A, Martinez-Cardús A, Musulén E, Aguilera R, Manzano JL, Neamati N, Abad A. A proteomic approach links decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer and in human cell lines. Mol Cancer Ther. 2009 Apr;8(4):771-8. doi: 10.1158/1535-7163.MCT-08-0882. PMID: 19372549.

  • Martinez-Balibrea E, Martínez-Cardús A, Musulén E, Ginés A, Manzano JL, Aranda E, Plasencia C, Neamati N, Abad A. Increased levels of copper efflux transporter ATP7B are associated with poor outcome in colorectal cancer patients receiving oxaliplatin-based chemotherapy. Int J Cancer. 2009 Jun 15;124(12):2905-10. doi: 10.1002/ijc.24273. PMID: 19296535.

  • Martinez-Cardús A, Martinez-Balibrea E, Bandrés E, Malumbres R, Ginés A, Manzano JL, Taron M, Garcia-Foncillas J, Abad A. Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer. Mol Cancer Ther. 2009 Jan;8(1):194-202. doi: 10.1158/1535-7163.MCT-08-0659. PMID: 19139129.

  • Martinez-Balibrea E, Abad A, Aranda E, Sastre J, Manzano JL, Díaz-Rubio E, Gómez-España A, Aparicio J, García T, Maestu I, Martínez-Cardús A, Ginés A, Guino E; Spanish Group for the Treatment of Digestive Tumours. Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer. Eur J Cancer. 2008 Jun;44(9):1229-37. doi: 10.1016/j.ejca.2008.03.025. PMID: 18448328.

  • Martinez-Balibrea E, Manzano JL, Martinez-Cardus A, Moran T, Cirauqui B, Catot S, Taron M, Abad A. Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan. Oncol Rep. 2007 Mar;17(3):637-45. PMID: 17273745.
  • ​Curcumin and angiogenesis; PI: Eva Martinez-Balirea; Funded by Roche Pharma.                                                                                     Goal: To study the effects of Curcumin on angiogenesis of CRC in order to consider this compound to be combined with antiangiogenic drugs.

  • Study of the CXC family of chemokines and their receptors as prognostic and/or predictive biomarkers of response and as possible therapeutic targets in colorectal cancer patients. (PI16/01800); PI Eva Martinez-Balibrea; Funded by ISCIII
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  • RESPONSE: Biomarkers and combinatorial drug targets for a personalized therapy for three major cancers. (PIE16/00011); Project coordinator: Marcus Buschbeck; PI Eva Martinez-Balibrea; Funded by ISCIII (Proyectos integrados de excelencia)                           Goal: By simulating treatments in culture, we will perform loss-of-function screens in order to identify genes encoding for transcriptional and chromatin affecting drug sensitivity in three major cancers including colorectal (PIs: Eva Martínez-Balibrea and Sonia Forcales, from Perucho’s lab).
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  • To study the role and function of CXC-chemokines and their receptors (serum levels, expression, genetic variants) in CRC and to evaluate them as possible serum biomarkers. A secondary objective proposes the study of circulating MDSCs in CRC patients.
​Polly Newcomb, Ulrike Peters: ISACC (International Survival Analysis in Colorectal Cancer), part of GECCO: https://www.fredhutch.org/en/labs/phs/projects/cancer-prevention/projects/gecco.html
Fred Hutchinson Cancer Research Center, Seattle, WA, USA