Genotype-dependent sensitivity of uveal melanoma cell lines to inhibition of B-Raf, MEK, and Akt kinases: rationale for personalized therapy.

Purpose: Inhibitors of B-Raf and MEK kinases hold promise for the management of cutaneous melanomas harboring BRAF mutations. BRAF mutations are rare in uveal melanomas (UMs), but somatic mutations in the G protein α subunits Gαq and Gα11 (encoded by GNAQ and GNA11, respectively) occur in a mutually exclusive pattern in ∼80% of UMs. The impact of B-Raf and MEK inhibitors on Gα-mutant UMs remains unknown.