Update on Hsp90 inhibitors in clinical trial.
Twenty-five years ago the first small molecule inhibitors of Hsp90 were identified. In the intervening years there has been dramatic progress in basic scientific understanding of the Hsp90 chaperone machinery and in the role of Hsp90 in malignancy. The first-in-class Hsp90 inhibitor 17-AAG entered into Phase I clinical trials in 1999. There are now 13 Hsp90 inhibitors in clinical trial, representing multiple drug classes, and hundreds of patients have been treated in adult oncology and pediatric oncology trials. This review will provide an overview of the clinical trial results thus far. In addition, pivotal issues in further development of Hsp90 inhibitors as anticancer drugs will be discussed.
Medical Oncology Branch, NCI, NIH, Bethesda, MD 20892, USA.
Y S
YS
Kim
S V
SV
Alarcon
S
S
Lee
M-J
MJ
Lee
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Giaccone
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L
Neckers
J B
JB
Trepel
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins