Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies

摘要: Increasing knowledge of the underlying signaling pathways and molecular defects involved in colorectal cancer growth or progression enabled discovery several prognostic predictive biomarkers, leading to development novel molecularly targeted therapies. The mitogen-activated protein kinase (MAPK) pathway plays a critical role progression. Mutations BRAF, principal effector Ras this cascade, are found 10 % play clear pathogenic role, particularly patients with metastatic disease. Intense efforts have therefore focused on targeting BRAF as an oncogenic driver, mixed early results. This article summarizes clinical features mutant cancer, BRAFV600E mutation initial trial results BRAFV600E, more recent preclinical insights into potential mechanisms resistance inhibition that now led number rationale-driven combination therapeutic strategies.