The results of clinical phase II and III trials evaluating the efficacy of these drugs in different types of tumours are awaited. Hsp90 inhibitors can be used as single agents or in combination with other targeted treatments or chemotherapy and radiotherapy. The best known of them, 17-AAG, has shown significant antitumour activity against a broad variety of cancers in preclinical studies, including breast, myeloma, melanoma, prostate and lung cancers. Biochemical and structural analysis of Hsp90 has revealed a complex mechanism of ATPase-coupled conformational changes and interactions with cochaperone proteins, which facilitate activation of Hsp90's diverse clientele. We will review the clinical data on Hsp90 inhibitors in different malignancies. AbstractHeat shock protein 90 (Hsp90) is a molecular chaperone essential for activating many signaling proteins in the eukaryotic cell. Under normal growth conditions, Hsp90 plays a major role in various aspects of the secretory pathway and cellular transport during environmental stress, Hsp90. Hsp90 inhibitors, derived from the natural compound geldanamycin, are attractive targets for anticancer drug development. Inhibition of Hsp90 leads to the degradation of known oncogene products, such as Her2, BRAF and others, leading to the simultaneous blockade of multiple oncogenic transduction pathways. A growing number of Hsp90 client proteins have been shown to be important for the development, proliferation and survival of several types of cancer. Hsp90 proteins are the best studied proteins of this family. Heat shock proteins are ubiquitous molecular chaperones involved in posttranslational folding, stability, activation and maturation of many proteins that are essential mediators of signal transduction and cell cycle progression.
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