An Update on BRAF Inhibitors and Other New Molecular Targets for the Treatment of Malignant Melanoma of the Skin

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the new molecular entities that are approved are reviewed here. Approved by FDA in 2011, vemurafenib (Zelboraf) is the first personalized targeted therapy for treatment of metastatic melanoma that acts by selectively inhibiting BRAFV600E. This has opened a new avenue for the discovery of targeted drug therapies for melanoma based on the principles of pharmacogenomics