Heat shock protein 90: A unique chemotherapeutic target

A large body of work spanning the past decade has identified the molecular chaperone heat shock protein 90 (Hsp90) as a critical modulator of an extensive network of cellular signaling pathways. Many of the processes overseen by Hsp90 are deregulated in tumor cells, including cell cycle control, gene transcription, and apoptotic signaling. Hsp90 inhibition offers the potential of accomplishing what most molecularly targeted anticancer therapies do not-the simultaneous disruption of multiple signaling events critical to tumor cell growth and survival. Indeed, small molecule inhibitors of Hsp90 function are actively being evaluated in the clinic as anticancer agents. In this review, we highlight the current understanding of Hsp90 biology as it relates to cancer and discuss the discovery, development, and clinical status of Hsp90 inhibitors as anticancer drugs. © 2006 Elsevier Inc. All rights reserved.