title: Targeting heat shock proteins 70/90 and proteasome for cancer therapy.
abstract: Recent progresses in cancer therapy suggest the importance of targeting more than one protein targets or signaling pathways. In events of stresses including the therapeutic treatments, damaged proteins are either repaired by heat shock proteins or ubiquitin-tagged for proteasome-dependent protein degradation. Heat shock proteins mediated protein protection and cell signaling, as well as the ubiquitin-proteasomal degradation are thus central to cellular homeostasis, and are reported to play substantial roles in tumor cells' rapid-metabolism and stimuli-resistance. The up-regulated heat shock protein 90 (HSP90), heat shock protein 70 (HSP70) and 26S proteasome in cancer cells have been thereby recognized as important drug targets and are under intensive studies in recent years. While most research focuses on each target in a separate manner, simultaneous inhibition of more than one target results in an enhanced efficacy, especially in single-drug-resistant cancer cell line. In this review, current development of chemical inhibitors for these three core targets is summarized respectively and the progress on related simultaneous inhibitions has been discussed. In a perspective view, combined inhibitions of HSP 90/70 and the 26S proteasome could be a promising approach in cancer therapy and may suggest a future direction for drug-screening.
authors.affiliation: Department of Chemistry, Washington University, St Louis, MO 63130, USA. rongshengwang@wustl.edu
authors.forename: R E
authors.initials: RE
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex