[Inhibitors of the heat shock protein 90 activity: a novel class of tumor radiosensitizers].
The 90 kDa heat shock protein (HSP90) is one of major chaperones of eukaryotes which catalyzes maturation and activation of its client proteins. Among the identified client proteins there are oncogene products, hormone or growth factor receptors and key components of signaling pathways responsible for the malignant growth of tumors or their resistance to chemotherapy and radiotherapy. In the case of inhibition of the HSP90 chaperone function, such proteins are inactivated and degraded soon that leads to simultaneous blocking several pathways essential for proliferation and survival of malignant cells; therefore, pharmacological inhibitors of the HSP90 chaperone activity could be used in anticancer therapy. At present, several HSP90 inhibitors are in preclinical testing or I-III Phase clinical trials as mono-agents or in combinations with other anticancer drugs or radiation. In the present review, all the data are summarized which characterize HSP90 inhibitors as effective radiosensitizers of tumor cells. Molecular mechanisms and selectivity of the radiosensitizing action of HSP90 inhibitors are here discussed as well as a possibility of their application to improve the outcome of radiotherapy.
A E
AE
Kabakov
V A
VA
Kudriavtsev
Iu M
IuM
Makarova
D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D018841:HSP90 Heat-Shock Proteins; D011838:Radiation-Sensitizing Agents