ARTICLE | Cover Story

Melanoma: three ways around BRAF inhibition

December 9, 2010 8:00 AM UTC

Independent research teams have identified three mechanisms by which melanoma can develop resistance to BRAF inhibitors,1,2 a promising class of therapeutics that include late-stage clinical compounds from Plexxikon Inc. and GlaxoSmithKline plc. The findings suggest that BRAF inhibitors will need to be combined with other types of drugs, although future studies will have to determine the relative frequency of each mechanism.

About 60% of melanomas express an activating mutation in the serine/threonine kinase BRAF that enables tumor cell growth and proliferation. The most advanced inhibitor of mutant BRAF is PLX4032 (R7204; RG7204) from Plexxikon and Roche. The compound is in Phase III testing. Phase II data showed that some patients whose melanoma initially responded to the compound later developed resistance.3,4...