Protein Reviews Volume 7, 2007, pp 422-450

Heat Shock Proteins in the Progression of Cancer

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The cohort of heat shock proteins (HSP) induced by cell stress becomes expressed at high levels in a wide range of tumors, and elevated levels of HSP are closely associated with a poor prognosis and treatment resistance. Increased HSP transcription in tumor cells is due both to loss of p53 function and elevated expression of proto-oncogenes such as HER2 and c-Myc and plays an essential role in tumorigenesis. The HSP family members overexpressed in cancer play overlapping, essential roles in tumor growth both by promoting autonomous cell proliferation and by inhibiting multiple death pathways. The HSP have thus become important and novel targets for rational anti-cancer drug design and HSP 90 inhibitors such as geldanomycin and 17-AAG are currently showing much promise in clinical trial while elevated HSP in tumors form the basis for chaperone-based immunotherapy.