Heat shock proteins in cancer: chaperones of tumorigenesis.
The heat shock proteins (HSPs) induced by cell stress are expressed at high levels in a wide range of tumors and are closely associated with a poor prognosis and resistance to therapy. The increased transcription of HSPs in tumor cells is due to loss of p53 function and to higher expression of the proto-oncogenes HER2 and c-Myc, and is crucial to tumorigenesis. The HSP family members play overlapping, essential roles in tumor growth both by promoting autonomous cell proliferation and by inhibiting death pathways. The HSPs have thus become targets for rational anti-cancer drug design: HSP90 inhibitors are currently showing much promise in clinical trials, whereas the increased expression of HSPs in tumors is forming the basis of chaperone-based immunotherapy.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. scalderw@bidmc.harvard.edu
Stuart K
SK
Calderwood
Md Abdul
MA
Khaleque
Douglas B
DB
Sawyer
Daniel R
DR
Ciocca
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D010641:Phenotype
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones