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Journal of Oncology
Volume 2010 (2010), Article ID 412985, 17 pages
http://dx.doi.org/10.1155/2010/412985
Review Article

Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls

Department of Cell & Molecular Pharmacology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA

Received 25 December 2009; Accepted 12 April 2010

Academic Editor: Sundaram Ramakrishnan

Copyright © 2010 J. E. Bohonowych et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90) provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1) Hsp90-mediated regulation of HIF/VEGF signaling, (2) chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3) Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4) consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.