17-AAG: mechanisms of antitumour activity

摘要

Heat-shock protein 90 (Hsp90) is a molecular chaperone involved in three-dimensional folding,intracellular translocation and degradation of multiple key regulatory proteins.Accumulated evidence has indicated an important role of Hsp90 in several signal transduction pathways that are deregulated in carcinogenesis.17-Allylamino-17-demethoxygeldanamycin (17-AAG),a selective inhibitor of Hsp90,is currently under clinical investigation in advanced malignancies in which Hsp90 client proteins are implicated.This article discusses the mechanistic evidence underlying 17-AAG's cytostatic,pro-apoptotic,antiangiogenic and anti-invasive properties that provide the basis for its antitumour activity and underscores its unique therapeutic potential as a multi-targeted agent,as opposed to most of the current-generation molecular therapeutics.