Innovating Works

antiCAFing

Financiado
Harnessing Stromal Fibroblasts to Reduce Resistance and Improve Colon Cancer The...
Refractory tumors and emergence of drug resistance are the most important challenges in cancer therapeutics. The non-cancerous determinants of therapeutic response and particularly the role of the tumor microenvironment (TME) in r... Refractory tumors and emergence of drug resistance are the most important challenges in cancer therapeutics. The non-cancerous determinants of therapeutic response and particularly the role of the tumor microenvironment (TME) in resistance are poorly understood. I previously described the crucial role of cancer-associated fibroblasts (CAFs) in key tumorigenic processes, including matrix remodeling, cancer cell invasion and growth. Importantly, these aggressive CAF phenotypes are controlled by mechanical reprogramming and mechanotransduction pathways. Within therapeutic resistance contexts, I hypothesize that preexistent and therapy-induced aberrant activation of mechanotransduction signaling in CAFs leads to the generation of refractory TMEs affecting cancer cell signaling and the behavior of accessory stromal cells such as endothelial and immune cells. As a result, tumors will present: (i) abnormal vasculature associated with reduced drug perfusion and chemotherapy efficacy; (ii) increased production of pro-survival signals affecting targeted therapy; and (iii) inactivation of cytolytic T cells and reduced responses to immunotherapy. I propose that CAF-based biomarkers will improve our capacity to identify patients most likely to respond to these therapeutics. In addition, targeting mechanotransduction in CAFs will significantly increase efficacy in non-responders. Focusing in colorectal cancer, I will use patient-derived CAFs as a tractable system and organ-on-chip, in vitro and preclinical models of CAF-mediated resistance, and combinatorial chemistry to systematically elucidate the molecular and biological features conferring CAFs their privileged therapy-resistance properties. This will illuminate novel and general mechanisms whereby TME characteristics influence tumorigenesis, and inform the development of refined biomarkers to stratify patients and next generation combinatorial therapies (including anti-CAF therapies) with reduced risk of recurrence. ver más
31/08/2027
CSIC
2M€
Perfil tecnológico estimado
Duración del proyecto: 60 meses Fecha Inicio: 2022-08-08
Fecha Fin: 2027-08-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-08-08
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2021-COG: ERC CONSOLIDATOR GRANTS
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 2-3 552M