Abstract | UNLABELLED: SIGNIFICANCE: A problem with most of the Hsp90 inhibitor drugs now in cancer clinic trials is that they potently activate Hsf1. This leads to an induction of heat shock proteins, many of which have a "pro-survival" role in that they help to protect cells from apopotosis. As the activation of Hsf1 requires TORC1, inhibitors of mTOR kinase could potentially block this activation of Hsf1 and be of value when used in combination drug therapies with Hsp90 inhibitors. However many of the mechanistic details of the TORC1 regulation of Hsf1, as well as the interplay between cellular resistances to rapamycin and to Hsp90 inhibitors, still remain to be resolved.
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Authors | Stefan H Millson, Peter W Piper |
Journal | Oncotarget
(Oncotarget)
Vol. 5
Issue 13
Pg. 5054-64
(Jul 15 2014)
ISSN: 1949-2553 [Electronic] United States |
PMID | 24970820
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antifungal Agents
- DNA-Binding Proteins
- Enzyme Inhibitors
- HSF1 protein, S cerevisiae
- HSP82 protein, S cerevisiae
- HSP90 Heat-Shock Proteins
- Heat-Shock Proteins
- Macrolides
- Saccharomyces cerevisiae Proteins
- TORC1 protein complex, S cerevisiae
- Transcription Factors
- PPT1 protein, S cerevisiae
- Phosphoprotein Phosphatases
- Tacrolimus Binding Protein 1A
- monorden
- Sirolimus
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Topics |
- Antifungal Agents
(pharmacology)
- Cell Division
(drug effects, genetics)
- DNA-Binding Proteins
(antagonists & inhibitors, genetics, metabolism)
- Enzyme Inhibitors
(pharmacology)
- HSP90 Heat-Shock Proteins
(antagonists & inhibitors, genetics, metabolism)
- Heat-Shock Proteins
(antagonists & inhibitors, genetics, metabolism)
- Macrolides
(pharmacology)
- Mutation
- Phosphoprotein Phosphatases
(genetics, metabolism)
- Saccharomyces cerevisiae
(drug effects, genetics, metabolism)
- Saccharomyces cerevisiae Proteins
(antagonists & inhibitors, genetics, metabolism)
- Sirolimus
(pharmacology)
- Tacrolimus Binding Protein 1A
(genetics, metabolism)
- Transcription Factors
(antagonists & inhibitors, genetics, metabolism)
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