Counteracting oxidative phosphorylation-mediated resistance of melanomas to MAPK pathway inhibition
نویسندگان
چکیده
Mitochondrial oxidative phosphorylation (OxPhos) induces resistance to MAPK pathway inhibitors in melanoma. However, therapeutic targeting of mitochondria is challenging. In a recent study, we showed that inhibition of mTOR kinase activity resensitized resistant melanomas by indirectly inhibiting OxPhos via a novel mechanism. Here, we discuss the implications of these findings.
منابع مشابه
Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma.
Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1α. Notably, all selumetinib-resistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inh...
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متن کاملInhibition of mTORC1/2 Overcomes Resistance to MAPK Pathway Inhibitors Mediated by PGC1a and Oxidative Phosphorylation in Melanoma
Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAFand NRASmutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1a. Notably, all selumetinibresistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inhibit...
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