Matches in SemOpenAlex for { <https://semopenalex.org/work/W4375955174> ?p ?o ?g. }
- W4375955174 abstract "MYC is a key oncogenic driver in multiple tumor types, but concomitantly endows cancer cells with a series of vulnerabilities that provide opportunities for targeted pharmacological intervention. For example, drugs that suppress mitochondrial respiration selectively kill MYC-overexpressing cells. Here, we unravel the mechanistic basis for this synthetic lethal interaction and exploit it to improve the anticancer effects of the respiratory complex I inhibitor IACS-010759. In a B-lymphoid cell line, ectopic MYC activity and treatment with IACS-010759 added up to induce oxidative stress, with consequent depletion of reduced glutathione and lethal disruption of redox homeostasis. This effect could be enhanced either with inhibitors of NADPH production through the pentose phosphate pathway, or with ascorbate (vitamin C), known to act as a pro-oxidant at high doses. In these conditions, ascorbate synergized with IACS-010759 to kill MYC-overexpressing cells in vitro and reinforced its therapeutic action against human B-cell lymphoma xenografts. Hence, complex I inhibition and high-dose ascorbate might improve the outcome of patients affected by high-grade lymphomas and potentially other MYC-driven cancers." @default.
- W4375955174 created "2023-05-10" @default.
- W4375955174 creator A5003067418 @default.
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- W4375955174 date "2023-05-09" @default.
- W4375955174 modified "2023-10-09" @default.
- W4375955174 title "Oxidative stress enhances the therapeutic action of a respiratory inhibitor in <scp>MYC</scp>‐driven lymphoma" @default.
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