Hsp90 inhibitors as novel cancer chemotherapeutic agents |
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| Institution: | 1. Department of Urology, Klinik Favoriten, Vienna, AUSTRIA;2. Sigmund Freud Private University, Vienna, AUSTRIA;1. Université de Paris, NF-κB, Différenciation et Cancer, F-75006 Paris, France;2. AP-HP, Hôpital Saint-Louis, Service Hémato-Oncologie, F-75010 Paris, France;1. Department of Pharmacy, College of Pharmacy, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C.;2. Department of Pharmacy, China Medical University Hospital, 2 Yude Road, Taichung, 40447, Taiwan, R.O.C.;3. Department of Public Health, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C.;4. Center for Drug Abuse and Addiction, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C. |
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| Abstract: | Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for the stability and function of multiple mutated, chimeric and over-expressed signaling proteins that promote the growth and/or survival of cancer cells. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1α (HIF-1α). Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and eventual degradation of Hsp90 client proteins, and they have shown promising antitumor activity in preclinical model systems. One Hsp90 inhibitor, 17-allylaminogeldanamycin (17AAG), is currently in phase I clinical trial. Because of the chemoprotective activity of several proteins that are Hsp90 clients, the combination of an Hsp90 inhibitor with a standard chemotherapeutic agent could dramatically increase the in vivo efficacy of the therapeutic agent. |
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