Targeted therapy resistance mechanisms and therapeutic implications in melanoma.

Although selective mutant BRAF inhibitors have revolutionized the treatment of metastatic melanoma, the magnitude and duration of their clinical benefit are significantly undermined by de novo and acquired resistance. Functional studies, molecular characterization of clinical samples, and clinical trials are providing insights into the landscape of resistance mechanisms in this disease. These findings have implications for the development of rational therapeutic approaches, and have identified several challenges that remain to be overcome if outcomes are to be improved in patients with metastatic melanoma.