During the past year, we confirmed that 17-AAG can inhibit melanoma cell proliferation by inducing the degradation of BRAF or BRAF and CRAF. We also demonstrated that 17-AAG can inhibit RAF kinase activity through an HSP90:BRAF complex when RAF does not undergo 17-AAG-dependent degradation. Finally, a melanoma cell line insensitive to 17-AAG was sensitive to inhibition of MITF, providing evidence that 17-AAG and MITF affect melanoma cell proliferation through the same pathway.
