Tumor Microenvironment and Biomarkers

In the tumor context, the microenvironment is defined as the set of normal cells, extracellular matrix, molecules and blood vessels that surrounds and support the tumor. Within this tumor microenvironment, the most numerous cells are fibroblasts, called cancer-associated fibroblasts (CAFs), which, through communication with tumor cells and the rest of the cells in the microenvironment, induce tumor development. In this cross-communication, exosomes play an important role as an element of communication between different types of cells, both those of the tumor environment itself and those of distal organs where metastatic nodules develop. Exosomes can be found in physiological fluids such as peripheral blood samples allowing the identification of disease-specific biomarkers by liquid biopsies.

The main objective of our group is focused on the identification of new biomarkers with diagnostic, prognostic and/or response value in colon cancer patients associated to the tumor microenvironment, and more specifically to CAFs. Colon cancer is one of the most frequent and lethal neoplasms both internationally and nationally, so the identification of new biomarkers that can be transferred and implemented as clinical tools to support decision making and management of these patients is a key point in the development of personalized medicine or personalized medicine.

More specifically, our objectives are focused on:  

- Establishment of primary cultures of CAFs/colonic mucosal fibroblasts (NFs) from patients: study of their ability to stimulate tumorogenesis. 
- Determination and validation of pro-tumorogenic mediators between primary cultures of CAFs/NFs and extracellular matrices derived from these and colon tumor cells or other cells from the tumor microenvironment.
- Study of the nucleic acid content of exosomes derived from primary cultures of CAFs/NFs. Effects of these exosomes on colon cancer tumor development.
- Identification of biomarkers in liquid biopsy exosomes (peripheral blood) of markers derived from CAFs and correlation with tumorogenic properties, pathological characteristics of the tumors and patient survival. 
- Development of mathematical models from computed tomography images for a correct classification of patients according to their probability of relapse.

We collaborate closely with clinicians at the Ramón y Cajal University Hospital to learn first-hand about the needs of colon cancer patients and the problems faced by physicians in the management of these patients. We contribute our experience in the field of molecular and cellular biology by developing translational research with a clear multidisciplinary character. Thus, our studies always involve the use of clinical samples as a starting point, guaranteeing the clinical relevance of the findings. The results generated contribute to clinical progress in the development of CAF-derived biomarkers and targeted therapies against these cells that may involve new therapeutic approaches.

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