Estudio evolutivo, mediante biopsia líquida, del genotipo tumoral de KRAS, NRAS y BRAF en pacientes con cáncer colorrectal metastásico RAS mutado tratados con fármacos antiangiogénicos

Abstract

Colorectal cancer (CRC) is an aggressive disease associated with a poor outcome in a subset of patients. Approximately 22% of CRCs are metastatic (mCRC) at initial diagnosis and about 70% will develop metastatic relapse (VanCutsem, Oliveira and Grp 2009b). More than 40% of primary colorectal tumors carry oncogene RAS mutations. With the arrival of directed therapies against epidermal growth factor receptor (EGFR) signaling pathway for patients without mutations in KRAS proto-oncogene, GTPase (KRAS), NRAS proto-oncogene, GTPase (NRAS) and BRAF proto-oncogene, serine/threonine kinase (BRAF) genes, overall survival has increased. The use of anti-angiogenic based chemotherapy has revolutionized mCRC treatment as well. However, the impact of anti-angiogenics on the molecular profile of patients with RAS-mutated tumors is unclear. It has been hypothesized that KRAS-mutated tumors treated with vascular-directed therapy might change to a wild-type KRAS status (Gazzaniga et al. 2017). Drug-induced hypoxia has been suggested as a possible explanation for this, and has been related to over expression of wild-type KRAS (Zeng et al. 2010). However, to date, only a few studies have examined in depth the consequences of these changes in the evolution of the disease...