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• W2801138103 abstract "Abstract Purpose: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design: Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated preclinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. Results: We found phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with phenformin, was highly efficacious in controlling tumor burden. However, more strikingly, pretreatment with phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Conclusions: Treatment of HCC cells in vitro with the biguanide phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Clin Cancer Res; 24(15); 3767–80. ©2018 AACR." @default.
• W2801138103 created "2018-05-17" @default.
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• W2801138103 date "2018-07-31" @default.
• W2801138103 modified "2023-10-12" @default.
• W2801138103 title "Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR" @default.
• W2801138103 cites W1495825745 @default.
• W2801138103 cites W1900079465 @default.
• W2801138103 cites W1974342793 @default.
• W2801138103 cites W1983240403 @default.
• W2801138103 cites W1994193851 @default.
• W2801138103 cites W1997003352 @default.
• W2801138103 cites W1998771362 @default.
• W2801138103 cites W2000336618 @default.
• W2801138103 cites W2002870649 @default.
• W2801138103 cites W2012442095 @default.
• W2801138103 cites W2017592190 @default.
• W2801138103 cites W2019455536 @default.
• W2801138103 cites W2022317327 @default.
• W2801138103 cites W2023461035 @default.
• W2801138103 cites W2025129086 @default.
• W2801138103 cites W2038733728 @default.
• W2801138103 cites W2039935344 @default.
• W2801138103 cites W2041957369 @default.
• W2801138103 cites W2044874695 @default.
• W2801138103 cites W2046216416 @default.
• W2801138103 cites W2051725201 @default.
• W2801138103 cites W2061472125 @default.
• W2801138103 cites W2065649212 @default.
• W2801138103 cites W2074847845 @default.
• W2801138103 cites W20749215 @default.
• W2801138103 cites W2082564115 @default.
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• W2801138103 cites W2089171551 @default.
• W2801138103 cites W2090664023 @default.
• W2801138103 cites W2090711760 @default.
• W2801138103 cites W2092340120 @default.
• W2801138103 cites W2094241924 @default.
• W2801138103 cites W2096201751 @default.
• W2801138103 cites W2096758996 @default.
• W2801138103 cites W2098912234 @default.
• W2801138103 cites W2101774229 @default.
• W2801138103 cites W2107561358 @default.
• W2801138103 cites W2107674876 @default.
• W2801138103 cites W2109600717 @default.
• W2801138103 cites W2117931978 @default.
• W2801138103 cites W2121077787 @default.
• W2801138103 cites W2126783165 @default.
• W2801138103 cites W2128965737 @default.
• W2801138103 cites W2132413659 @default.
• W2801138103 cites W2133423870 @default.
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• W2801138103 cites W2140525205 @default.
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• W2801138103 cites W2171402611 @default.
• W2801138103 cites W2174118934 @default.
• W2801138103 cites W218534859 @default.
• W2801138103 cites W2269336718 @default.
• W2801138103 cites W2286842342 @default.
• W2801138103 cites W2326190830 @default.
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• W2801138103 doi "https://doi.org/10.1158/1078-0432.ccr-18-0177" @default.
• W2801138103 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29691292" @default.
• W2801138103 hasPublicationYear "2018" @default.
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