Resistance, chemotherapy and predictive biomarkers
Martínez-Balibrea’s Lab

Colorectal cancer (CRC), being the most prevalent form of cancer, stands as the second leading cause of cancer-related mortality in Spain. Despite the existence of various preventive campaigns facilitating the early detection of CRC, patients are usually diagnosed at an advanced stage of the disease. Treatment for these patients typically involves a combination of chemotherapy and anti-target drugs, aiming to diminish the tumour burden in order to operate the metastases (significantly extending survival rates) or improve symptomatology prolonging life (and its quality) as much as possible. Despite the significant advancements in the field of oncology, immunotherapies, unfortunately, demonstrate effectiveness in less than 5% of colorectal cancer cases.

One of the main problems in clinical practice is the emergence of treatment resistance, affecting almost all of our treated patients. The primary goal of our group is to understand the underlying mechanisms of this resistance and to identify predictive biomarkers associated with treatment response. Our research efforts are concentrated on the identification of tumour vulnerabilities in order to facilitate the utilization of alternative existing treatments or the development of new chemotherapeutic agent combination.

Our research is focused on the identification of predictive biomarkers to improve treatment selection. To attain this objective, we are investigating specific somatic polymorphisms within genes implicated in pharmacodynamics and pharmacokinetics processes that modulate the efficacy of particular chemotherapeutic drugs or their associated toxicities. Additionally, we are studying tumour gene and/or protein expression patterns derived from colorectal cancer patients’ samples. This analysis aims to decipher potential correlations with chemotherapy resistance, helping us to identify clinical biomarkers essential for treatment selection.

To deeply understand the mechanisms involved in the development of acquired resistance to various anticancer therapies, we developed and implemented in vitro and ex vivo models in our laboratory. Based on these experimental models, we study alterations, using high-throughput techniques, in the profiles of gene and protein expressions, alongside other changes, such as modifications in DNA-methylation patterns, associated with the emergence of resistance subsequent to treatment. This exploration of the molecular landscape helps us to elucidate potential mechanisms responsible for the acquisition of resistance to chemotherapeutics, defining new putative predictive biomarkers that allows us to identify innovative therapeutic intervention capable of reversing this chemoresistance

The most recent projects in which our laboratory is currently involved include:

Modelling immunotherapy response and toxicity in cancer (IMMUNO-model)

PI: Eva Martinez-Balibrea

Funding agency: COST (European Cooperation in Science and Technology) Association
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 

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: 2020
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