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Molecular Dynamics Simulations of Hsp90 with an Eye to Inhibitor Design
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Pharmaceuticals 2012, 5(9), 1008-1020;

Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer

Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, 80 Vas. Sofias Ave, 11528 Athens, Greece
Author to whom correspondence should be addressed.
Received: 19 July 2012 / Revised: 30 August 2012 / Accepted: 10 September 2012 / Published: 12 September 2012
(This article belongs to the Special Issue Hsp90 Inhibitors)
Full-Text   |   PDF [190 KB, uploaded 12 September 2012]


Hsp90 is an abundant protein in mammalian cells. It forms several discrete complexes, each containing distinct groups of co-chaperones that assist protein folding and refolding during stress, protein transport and degradation. It interacts with a variety of proteins that play key roles in breast neoplasia including estrogen receptors, tumor suppressor p53 protein, angiogenesis transcription factor HIF-1alpha, antiapoptotic kinase Akt, Raf-1 MAP kinase and a variety of receptor tyrosine kinases of the erbB family. Elevated Hsp90 expression has been documented in breast ductal carcinomas contributing to the proliferative activity of breast cancer cells; whilst a significantly decreased Hsp90 expression has been shown in infiltrative lobular carcinomas and lobular neoplasia. Hsp90 overexpression has been proposed as a component of a mechanism through which breast cancer cells become resistant to various stress stimuli. Therefore, pharmacological inhibition of HSPs can provide therapeutic opportunities in the field of cancer treatment. 17-allylamino,17-demethoxygeldanamycin is the first Hsp90 inhibitor that has clinically been investigated in phase II trial, yielding promising results in patients with HER2-overexpressing metastatic breast cancer, whilst other Hsp90 inhibitors (retaspimycin HCL, NVP-AUY922, NVP-BEP800, CNF2024/BIIB021, SNX-5422, STA-9090, etc.) are currently under evaluation. View Full-Text
Keywords: hsp90; breast cancer; 17-allylamino-17-demethoxygeldanamycin hsp90; breast cancer; 17-allylamino-17-demethoxygeldanamycin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Zagouri, F.; Bournakis, E.; Koutsoukos, K.; Papadimitriou, C.A. Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer. Pharmaceuticals 2012, 5, 1008-1020.

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