Preclinical validations have shown compelling responses to HSP90 inhibition in GIST, in vitro and in vivo: KIT oncoproteins are rapidly degraded after treatment with a variety of HSP90 inhibitors, and result in anti-proliferative and pro-apoptotic consequences.29,30 Although constitutively active KIT oncoproteins require chaperone HSP90 and are potently inactivated by HSP90 inhibitors, clinical trials in GIST patients still are underway because of toxicity resulting from concomitant inactivation of various other HSP90 client proteins, beyond KIT and PDGFRA. This evidence concerns the gene PDGFRA and gastrointestinal stromal tumor.