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Targeting Heat Shock Proteins 70/90 and Proteasome for Cancer Therapy

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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' rapidmetabolism 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.

Keywords: 26S proteasome; Heat shock protein 90 (HSP90); cancer; clinical trials; heat shock protein 70 (HSP70); proteasomal degradation; simultaneous inhibition

Document Type: Research Article


Publication date: September 1, 2011

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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