Optimizing the treatment of BRAF mutant melanoma

Selective inhibitors of the kinases BRAF and MEK for the treatment of patients with otherwise refractory BRAF mutant melanoma have demonstrated impressive efficacy, and combination treatment with these agents may prove to be even more effective. However, these drugs are not curative, mainly because of the relatively rapid development of drug resistance. Furthermore, they can produce undesired, and even unanticipated, side effects, including the emergence of neoplastic lesions harboring activating RAS mutations. Two recent reports reveal new considerations for the optimal approach to targeting this key oncogenic pathway in melanoma, highlighting the importance of combination treatment and therapeutic scheduling.