BRAF and Melanoma: Taking it Personally

Hensin Tsao, MD, PhD

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This trial has been widely publicized, and the general enthusiasm seems warranted. PLX4032 is the most selective and effective targeted agent against melanoma to date, although it is not the first anti-BRAF compound to undergo clinical trials. The results have to be interpreted in context. For instance, most acral lentiginous and mucosal melanomas have KIT rather than BRAF mutations and would not respond to PLX4032. Some in vitro evidence suggests that BRAF-normal melanoma cells may actually be stimulated by PLX4032.

In an era of personalized therapy, the genetics of a patient's melanoma will dictate treatment. Careful tumor genotyping will become commonplace. KIT-mutated, BRAF-mutated and NRAS-mutated melanomas will require completely different regimens, so histological and molecular diagnostics will be important. Even with profound responses such as those observed here, many melanomas relapse; therefore, resistance mechanisms have become the focus of intense research, and additional drugs may be needed to fully tame metastatic melanoma.

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