Investigative ophthalmology & visual science
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Invest. Ophthalmol. Vis. Sci. · Jun 2008
17-AAG and 17-DMAG-induced inhibition of cell proliferation through B-Raf downregulation in WT B-Raf-expressing uveal melanoma cell lines.
The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) has been shown to have promising results in antitumor activity through the degradation of the activated V600E mutant of B-Raf (V600E B-Raf) in cutaneous melanoma cell lines. It has different effects, however, on the wild-type form of B-Raf (WT B-Raf), according to the WT B-Raf activation levels in the tumor cells. Uveal melanoma cells express WT B-Raf and only rarely express V600E B-Raf. This study was conducted to investigate the effects of HSP90 inhibition on uveal melanoma cell lines. ⋯ These results suggest that targeting HSP90 in tandem with c-Kit inhibition may be a promising therapeutic approach to uveal melanoma.