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

Abstract

Increasing knowledge of the underlying signaling pathways and molecular defects involved in colorectal cancer growth or progression enabled the discovery of several prognostic and predictive biomarkers, leading to the development of novel molecularly targeted therapies. The mitogen-activated protein kinase (MAPK) signaling pathway plays a critical role in colorectal cancer progression. Mutations in BRAF, a principal effector of Ras in this signaling cascade, are found in 10 % of colorectal cancer and play a clear pathogenic role, particularly in patients with metastatic disease. Intense efforts have therefore focused on targeting BRAF as an oncogenic driver, with mixed early results. This ar..