Targeting chaperones in transformed systems--a focus on Hsp90 and cancer.
The molecular chaperone Hsp90 is a protein with important roles in maintaining the functional stability and viability of cells under a transforming pressure. Cancer cells harbour mutated oncogenic proteins or proteins with dysregulated function and the chaperone is required to maintain their folded and functionally active conformation. In addition, by chaperoning key proteins such as Raf-1, Akt, survivin and hTERT, Hsp90 regulates signalling pathways necessary for the growth, survival and limitless replicative potential of most tumours. Important elements of the apoptotic pathways are also regulated by Hsp90. Overall, these characteristics propose Hsp90 as an important target of whose inhibition may aim at a wide-range of oncogenic transformations. Several years into Hsp90 research have shed light into the feasibility, but also the limitations, of such an approach. In this review, the authors present the current understanding on the relevance and possibility of translating Hsp90 inhibitors into therapeutic agents in cancer therapy.
Chiosis
Gabriela
G
Programme in Molecular Pharmacology and Chemistry, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Box 482, New York, NY 10021, USA. chiosisg@mskcc.org
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones