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Here, this study reports two metabolism\u2010based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis\n                    <jats:sup>+<\/jats:sup>\n                    \/ketolysis\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) and ketolytic (glycolysis\n                    <jats:sup>+<\/jats:sup>\n                    \/ketolysis\n                    <jats:sup>+<\/jats:sup>\n                    ), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone\u2010containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53\u2010mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202201992","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:41:24Z","timestamp":1661722884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Metabolism\u2010Based Molecular Subtyping Endows Effective Ketogenic Therapy in p53\u2010Mutant Colon Cancer"],"prefix":"10.1002","volume":"9","author":[{"given":"Meng","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Radiation and Medical Oncology Hubei Key Laboratory of Tumor Biological Behaviors Hubei Clinical Cancer Study Center Zhongnan Hospital of Wuhan University  Wuhan 430071 China"},{"name":"Department of Gastrointestinal Surgery\/ Department of Clinical Nutrition Beijing 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