Chaperoning the Cancer: The Proteostatic Functions of the Heat Shock Proteins in Cancer.
BACKGROUND
Protein homeostasis (proteostasis) is vital for the survival of cells in physiological and pathological conditions. Particularly, cancer cells are in constant state of cellular stress due to rapid proliferation and decreased quality control in proteosynthesis and therefore, are exceedingly dependent on the homeostasis pathways. Among the complex biological mechanisms regulating proteostasis are the highly conserved molecular chaperones, heat shock proteins (HSPs). HSPs assist cell survival by catalysing the proper folding of proteins, modulation of the apoptotic machinery and finally regulating the protein degradation machinery, providing either the stability or the degradation of selected proteins under stress conditions. Inevitably, HSPs are upregulated in malignancies and participate in different hallmarks of cancer, with indispensable roles in the onset and progression of the disease. Moreover, high levels of HSPs contribute to poor prognosis and treatment resistance in various cancers. Therefore these molecular chaperones present as attractive targets for anti-cancer therapy.


OBJECTIVE
This review describes how HSPs regulate different hallmarks of cancer and provides an overview on the most relevant patents which have recently appeared in the literature.


METHODS
The patents were extracted from Google Patents (2012-2016) while the clinical trial results were mined from www.clinicaltrial.gov.


CONCLUSIONS
Review of literature shows that the proteostatic functions of HSPs can modify different hallmarks of cancer. Moreover, targeting HSPs (notably HSP27, HSP70 and HSP90) exhibited positive results in clinical trials so far. However, more studies should be designed to optimize the efficacy of mono or combination therapy in various malignancies.
Sepideh
S
Vahid
Daksh
D
Thaper
Department of Urologic science, University of British Columbia, The Vancouver Prostate Centre, 2660 Oak Street, Vancouver BC V6H3Z6. Canada.
Amina
A
Zoubeidi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic / Q000379:methods; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010330:Patents as Topic; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones
Cancer therapeutics; HSP; chaperons; hallmarks of cancer; proteostasis