title: Hsp90 inhibitor as a sensitizer of cancer cells to different therapies (review).
abstract: Hsp90 is a molecular chaperone that maintains the structural and functional integrity of various client proteins involved in signaling and many other functions of cancer cells. The natural inhibitors, ansamycins influence the Hsp90 chaperone function by preventing its binding to client proteins and resulting in their proteasomal degradation. N- and C-terminal inhibitors of Hsp90 and their analogues are widely tested as potential anticancer agents in vitro, in vivo as well as in clinical trials. It seems that Hsp90 competitive inhibitors target different tumor types at nanomolar concentrations and might have therapeutic benefit. On the contrary, some Hsp90 inhibitors increased toxicity and resistance of cancer cells induced by heat shock response, and through the interaction of survival signals, that occured as side effects of treatments, could be very effectively limited via combination of therapies. The aim of our review was to collect the data from experimental and clinical trials where Hsp90 inhibitor was combined with other therapies in order to prevent resistance as well as to potentiate the cytotoxic and/or antiproliferative effects.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, 040 01 Košice, Slovak Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Solárová
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, 040 01 Košice, Slovak Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Mojžiš
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, 040 01 Košice, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D001665:Binding Sites; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D000255:Adenosine Triphosphate; C001277:geldanamycin