Colorectal cancer is the most common cancer and represents the second leading cause of cancer deaths in Spain. Patients with metastatic disease are usually treated with a combination of chemotherapy and anti-target drugs with the intention of reducing the tumour burden in order to operate the metastases (which translates into a considerable increase in survival) or improve symptomatology and prolong life as much as possible. Although immunotherapies have been a breakthrough in the field of oncology, they are effective in less than 5% of colorectal cancer cases.

One of the biggest problems in achieving clinicians' objectives is the development of resistance to treatments, which sooner or later affects almost all patients. This research group investigates how and why colorectal tumours become resistant to conventional treatments with the aim of finding predictive markers of response and identifying tumour vulnerabilities that allow the use of alternative existing treatments or develop new ones. The group also investigates why immunotherapy is ineffective in this type of cancer and how this situation can be reversed.

The researchers of this group do so by using pre-clinical models and samples from the patients. Their ultimate goal is to develop new tools for personalised medicine that improve patients' survival and quality of life.

Keywords: Resistance, chemotherapy, colorectal cancer, biomarkers, pre-clinical models, immuno-oncology.

Resistance, chemotherapy and predictive biomarkers research group

Research lines

Deciphering mechanisms of resistance to treatment in colorectal cancer

Finding predictive biomarkers for treatment selection

  • To study somatic genetic polymorphisms within genes involved in pharmacodynamics and pharmacokinetics processes affecting the effectiveness of a given chemotherapeutic drug or its related toxicity.
  • To study tumour gene and/or protein expression patterns that could be associated with resistance to chemotherapy and that could serve as clinical biomarkers to select treatments.

Development and implementation of in vitro and ex vivo models of acquired resistance to different anti-cancer therapies

  • To study changes in patterns of gene or protein expression and DNA-methylation associated with resistance acquisition by using high-throughput techniques.
  • To elucidate the mechanisms responsible for resistance acquisition to chemotherapeutics and define new putative predictive biomarkers.
  • To identify new ways of therapeutic intervention able to revert this chemoresistance.

Active projects

Modelling immunotherapy response and toxicity in cancer

PI: Eva Martinez-Balibrea
Funding agency: IMMUNO-model COST Action - EU
Agency code: CA21135
Start date: 01/10/2022
End date: 31/12/2026

SPOT & HIT: Enabling personalized colorectal cancer management by coupling unified genetic and epigenetic testing to organoidbased treatment screening

Jordi Barretina, coordinator of WP1 and WP3
Funding agency: Ministerio de Ciencia e Innovación
Start date: 01/12/2022
End date: 30/11/2025

Integrating Translational Research in Gastric Cancer. Grupo TTD

Cinta Hierro, team member
Funding agency: Ministerio de Ciencia e Innovación
Start date: 01/01/2023
End date: 31/12/2023

Modelling immunotherapy response and toxicity in cancer

PI: Eva Martinez-Balibrea
Funding agency: IMMUNO-model COST Action - EU
Agency code: CA21135
Start date: 01/10/2022
End date: 31/12/2026

Systematic analysis of tumor vulnerabilities conferred by chromatin regulators loss in colorectal cancer

PI: Eva Martinez-Balibrea
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI20/01183
Start date: 01/01/2021
End date: 31/12/2023

Implementation of a comprehensive translational research platform within the framework of early clinical trials: the INSPECTA project

Eva Martinez-Balibrea, team member
Funding agency: Fundacion Merck Salud
Start date: 2030
End date: 2023

Remodelers of the extracellular matrix: association with lymphocytic infiltration and applicability as markers of response to immunotherapy in colon and rectal cancer

Eva Martinez-Balibrea, team member
Funding agency: Fundación Mutua Madrileña
Start date: 2020
End date: 2023

Degrading Cdk5 for treatment of colorectal cancer

PI: Eva Martinez-Balibrea
Funding agency: Fundación Científica Asociación Española Contra el Cáncer (AECC)
Start date: 01/12/2020
End date: 30/06/2023

Scientific publications

Bernat-Peguera A, Trigueros M, Ferrando-Díez A, Ibáñez C, Bystrup S, Martínez-Cardús A, Margelí M, Martínez-Balibrea E. Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data. Breast. 2022 Apr;62:1-9. DOI: 10.1016/j.breast.2022.01.007.

Layos L, Martínez-Balibrea E, Ruiz de Porras V. Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients? Int J Mol Sci. 2022 Nov 14;23(22):14058. DOI: 10.3390/ijms232214058.

Ruiz de Porras V, Bystrup S, Cabrero-de Las Heras S, Musulén E, Palomero L, Alonso MH, Nieto R, Arango D, Moreno V, Queralt C, Manzano JL, Layos L, Bugés C, Martinez-Balibrea E. Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients. Cancers (Basel). 2019 Oct 11;11(10):1540. DOI: 10.3390/cancers11101540.

Cabrero-de Las Heras S, Martínez-Balibrea E. CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer. World J Gastroenterol. 2018 Nov 14;24(42):4738-4749. DOI: 10.3748/wjg.v24.i42.4738.

Abad A, Martínez-Balibrea E, Viéitez JM, Alonso-Orduña V, García Alfonso P, Manzano JL, Massutí B, Benavides M, Carrato A, Zanui M, Gallego J, Grávalos C, Conde V, Provencio M, Valladares-Ayerbes M, Salazar R, Sastre J, Montagut C, Rivera F, Aranda E. Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based randomized phase II trial. Ann Oncol. 2018 Feb 1;29(2):439-444. DOI: 10.1093/annonc/mdx737.

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 Locoregional Cancer. Gastroenterology. 2016 Nov;151(5):961-972. DOI: 10.1053/j.gastro.2016.08.001.

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.

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.

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.


- Investigación, Proyectos,

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La red IMMUNO-model ha reunido a investigadores e innovadores de todo el mundo para fomentar la investigación en inmuno-oncología a través del avance en el desarrollo e implementación de modelos preclínicos. Esta iniciativa está financiada por el programa de Cooperación Europea en Ciencia y Tecnología (COST).

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