Targeting HSP90 for cancer therapy.
Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Heat-shock proteins are increased in many solid tumours and haematological malignancies. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of HSP90. Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. This review provides an overview of the HSP chaperone machinery and the structure and function of HSP90. We also highlight the key oncogenic proteins that are regulated by HSP90 and describe how inhibition of HSP90 could alter the activity of multiple signalling proteins, receptors and transcriptional factors implicated in carcinogenesis.
Mahalingam
D
D
Institute for Drug Development, Cancer Research and Therapy Centre at the University of Texas Health Science Centre, San Antonio, TX 78229, USA.
Swords
R
R
Carew
J S
JS
Nawrocki
S T
ST
Bhalla
K
K
Giles
F J
FJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins