BRAF Inhibitors in Metastatic Colorectal Cancer and Mechanisms of Resistance: A Review of the Literature

SIMPLE SUMMARY: The MAP kinases pathway has shown a key role in the pathogenesis of colorectal cancer. The development of targeted therapy against BRAF-mutated tumors is changing the management of advanced disease. A proper understanding of the mechanisms of acquired resistance is essential to optimize the results of systemic treatment. We aim to review the current knowledge and potential fields of research regarding the use of BRAF inhibitors in metastatic colorectal tumors. ABSTRACT: Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.