Mécanismes de résistance aux inhibiteurs de BRAF

Aims. - It is essential to better understand the mechanisms of resistance to targeted anti-BRAFtherapies in order to increase both response rates and the duration of clinical response totreatment. This literature review describes the signaling pathways involving BRAF and presentsrecent data from clinical trials with these molecules. Furthermore, we aim to describe the mainresistance mechanisms linked with targeted anti-BRAF therapies.

Context. - In patients with melanoma positive for the BRAF V600 mutation, clinical responseto specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms ofprogression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibitlong-lasting response to these targeted therapies.

Methods. - The keywords (resistance, BRAF, melanoma, targeted therapy, vemurafenib, anddabrafenib) were used to extract relevant articles in the Medline/Pubmed database publishedbefore 31 January 2014.

Discussion. - Improved knowledge and understanding of the mechanisms of resistance to targe-ted anti-BRAF therapies should enable the development of new therapeutic strategies in orderto overcome such resistance and allow more significant and sustained response rates to beachieved among melanoma patients.