Vemurafenib: the first drug approved for BRAF-mutant cancer

The BRAF oncogene is found in 6–8% of all solid tumours, including about half of all melanomas.Scaffold-based drug discovery was used to discover inhibitors of the BRAF oncogene.Vemurafenib was identified as a selective inhibitor of oncogenic BRAF.Preclinical studies supported the testing of the compound in patients with metastatic melanoma.Significant clinical benefit was documented in patients with metastatic melanoma, validating the BRAF oncogene as a driver of these tumours. This led to regulatory approval of vemurafenib in the United States and Europe for the treatment of BRAF-mutant metastatic melanoma.During the development of vemurafenib, an important unexpected finding was linked to some of the side effects: the RAF inhibitor paradox denotes inhibitor-induced RAF pathway activation in cells with elevated RAS signalling.Future studies will explore the efficacy of vemurafenib in other tumours bearing the BRAF oncogene, and in combinations with other anticancer agents to improve the degree and durability of clinical benefit.