Hsp90 inhibitors as promising agents for radiotherapy

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 88; no. 3; pp. 241 - 247
• Main Authors: Kabakov, Alexander E., Kudryavtsev, Vladimir A., Gabai, Vladimir L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-03-2010; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Clinical Trials, Phase I as Topic; Combined Modality Therapy; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Human Genetics; Humans; Internal Medicine; Molecular Medicine; Neoplasms - drug therapy; Neoplasms - radiotherapy; Radiation-Sensitizing Agents - chemistry; Review; Cancer cell; Radiosensitizers; Radiation response; Client proteins; Chaperone
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-009-0562-0

The 90-kD heat shock protein (Hsp90) is an abundant molecular chaperone catalyzing maturation and activation of client proteins. A number of the Hsp90 client proteins are components of cancer cell-associated signaling pathways that ensure unlimited growth of tumors and their resistance to chemotherapy and radiotherapy. Upon inhibition of the Hsp90 chaperone function, such client proteins are destabilized and degraded which disrupts multiple pathways essential for tumor cell survival; hence, pharmacological Hsp90 inhibitors could be applied in anticancer therapy. Several Hsp90-inhibiting compounds are currently tested in preclinical or phase I–III clinical trials as single anticancer agents or in combination with conventional drugs and radiation. The present review summarizes the data characterizing Hsp90 inhibitors as agents that sensitize human tumors to irradiation which may improve the outcome of radiotherapy. We also discuss molecular mechanisms of the Hsp90 inhibition-induced radiosensitization and its selectivity toward cancer cells.