{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:47:10Z","timestamp":1789645630731,"version":"4.0.0"},"reference-count":177,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI20\/01107"],"award-info":[{"award-number":["PI20\/01107"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NEN Association\/Nico contra el cancer infantil","award":["2017 \u2013 PVR00157"],"award-info":[{"award-number":["2017 \u2013 PVR00157"]}]},{"name":"Neuroblastoma Foundation","award":["PVR00166"],"award-info":[{"award-number":["PVR00166"]}]},{"name":"Asociaci\u00f3n Fundaci\u00f3n Espa\u00f1ola contra el C\u00e1ncer, JAP-AECC","award":["2018\/150"],"award-info":[{"award-number":["2018\/150"]}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00484"],"award-info":[{"award-number":["CB16\/12\/00484"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["PI20\/01107"],"award-info":[{"award-number":["PI20\/01107"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.<\/jats:p>","DOI":"10.3390\/metabo11050264","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-4945","authenticated-orcid":false,"given":"Ezequiel","family":"Monferrer","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical School, INCLIVA Biomedical Health Research Institute, University of Valencia, 46010 Valencia, Spain"},{"name":"Low Prevalence Tumors, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Vieco-Mart\u00ed","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, INCLIVA Biomedical Health Research Institute, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"L\u00f3pez-Carrasco","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, INCLIVA Biomedical Health Research Institute, University of Valencia, 46010 Valencia, Spain"},{"name":"Low Prevalence Tumors, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Fari\u00f1as","sequence":"additional","affiliation":[{"name":"Ynmun Group, Institute of Clinical Immunology and Infectious Diseases, 29004 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Abanades","sequence":"additional","affiliation":[{"name":"Integrative and Conscious Health Institute, 08008 Barcelona, Spain"},{"name":"International College of Human Nutrition and Functional Medicine, 08001 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"de la Cruz-Merino","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-7459","authenticated-orcid":false,"given":"Rosa","family":"Noguera","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, INCLIVA Biomedical Health Research Institute, University of Valencia, 46010 Valencia, Spain"},{"name":"Low Prevalence Tumors, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"\u00c1lvaro Naranjo","sequence":"additional","affiliation":[{"name":"Low Prevalence Tumors, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Pathology, Verge de la Cinta Hospital of Tortosa, Catalan Institute of Health, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43500 Tortosa, Spain"},{"name":"Department of Basic Medical Sciences, Medical School, Rovira i Virgili University, 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, X., Chen, S., and Yu, D. (2020). Metabolic reprogramming of chemoresistant cancer cells and the potential significance of metabolic regulation in the reversal of cancer chemoresistance. Metabolites, 10.","DOI":"10.3390\/metabo10070289"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Elia, I., and Haigis, M.C. (2021). Metabolites and the tumour microenvironment: From cellular mechanisms to systemic metabolism. Nat. Metab., 3.","DOI":"10.1038\/s42255-020-00317-z"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-7075-7-7","article-title":"Cancer as a metabolic disease","volume":"7","author":"Seyfried","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1158\/0008-5472.CAN-16-0266","article-title":"Metabolic plasticity as a determinant of tumor growth and metastasis","volume":"76","author":"Dupuy","year":"2016","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"De Berardinis, R.J., and Chandel, N.S. (2016). Fundamentals of cancer metabolism. Sci. Adv., 2.","DOI":"10.1126\/sciadv.1600200"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/15384101.2016.1271635","article-title":"The new anticancer era: Tumor metabolism targeting","volume":"16","author":"Borriello","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1007\/BF01504608","article-title":"\u00dcber den Stoffwechsel der Carcinomzelle","volume":"12","author":"Warburg","year":"1924","journal-title":"Naturwissenschaften"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2967\/jnumed.108.054205","article-title":"18F-FDG PET and PET\/CT in the evaluation of cancer treatment response","volume":"50","author":"Ell","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1007\/s13277-013-1496-2","article-title":"Hexokinase 2 overexpression promotes the proliferation and survival of laryngeal squamous cell carcinoma","volume":"35","author":"Chen","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Roda, N., Gambino, V., and Giorgio, M. (2020). Metabolic Constrains Rule Metastasis Progression. Cells, 9.","DOI":"10.3390\/cells9092081"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1158\/1078-0432.CCR-14-0990","article-title":"Imaging intratumor heterogeneity: Role in therapy response, resistance, and clinical outcome","volume":"21","author":"Rose","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/1878-0261.12639","article-title":"Metabolism-associated molecular classification of hepatocellular carcinoma","volume":"14","author":"Yang","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, R., Liang, F., Zhang, L., and Liang, X. (2020). Identification of Metabolism-Associated Prostate Cancer Subtypes and Construction of a Prognostic Risk Model. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.598801"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, M., Wang, H.Z., Peng, R.Y., Xu, F., Wang, F., and Zhao, Q. (2020). Metabolism-Associated Molecular Classification of Colorectal Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.602498"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.semcdb.2019.05.016","article-title":"Reconciling environment-mediated metabolic heterogeneity with the oncogene-driven cancer paradigm in precision oncology","volume":"98","author":"Corbet","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-3-319-77736-8_5","article-title":"The intricate metabolism of pancreatic cancers","volume":"Volume 1063","author":"Camelo","year":"2018","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Martinez, C.A., and Scafoglio, C. (2020). Heterogeneity of glucose transport in lung cancer. Biomolecules, 10.","DOI":"10.3390\/biom10060868"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cappelletti, V., Iorio, E., Miodini, P., Silvestri, M., Dugo, M., and Daidone, M.G. (2017). Metabolic Footprints and Molecular Subtypes in Breast Cancer. Dis. Markers, 2017.","DOI":"10.1155\/2017\/7687851"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5236","DOI":"10.1158\/1078-0432.CCR-07-5252","article-title":"Intratumoral metabolic heterogeneity of cervical cancer","volume":"14","author":"Kidd","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.addr.2020.07.013","article-title":"Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention","volume":"159","author":"Butler","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s11914-018-0453-9","article-title":"The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone","volume":"16","author":"Diedrich","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, W., Bai, L., Li, W., and Cui, J. (2020). The Lipid Metabolic Landscape of Cancers and New Therapeutic Perspectives. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.605154"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101055","DOI":"10.1016\/j.plipres.2020.101055","article-title":"Lipids in the tumor microenvironment: From cancer progression to treatment","volume":"80","author":"Corn","year":"2020","journal-title":"Prog. Lipid Res."},{"key":"ref_24","first-page":"3984","article-title":"Metabolic Remodeling Induced by Adipocytes: A New Achilles\u2019 Heel in Invasive Breast Cancer?","volume":"27","author":"Milhas","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1080\/14728222.2017.1381087","article-title":"Fatty acid synthase (FASN) as a therapeutic target in breast cancer","volume":"21","author":"Menendez","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1021\/jm501543u","article-title":"Repositioning proton pump inhibitors as anticancer drugs by targeting the thioesterase domain of human fatty acid synthase","volume":"58","author":"Fako","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1073\/pnas.1808834116","article-title":"Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer","volume":"116","author":"Zadra","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2217\/fon.10.11","article-title":"Fatty acid synthase as a potential therapeutic target in cancer","volume":"6","author":"Flavin","year":"2010","journal-title":"Futur. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gil-De-g\u00f3mez, L., Balgoma, D., and Montero, O. (2020). Lipidomic-based advances in diagnosis and modulation of immune response to cancer. Metabolites, 10.","DOI":"10.3390\/metabo10080332"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1007\/s13277-013-1510-8","article-title":"Fatty acid synthase (FASN) levels in serum of colorectal cancer patients: Correlation with clinical outcomes","volume":"35","author":"Long","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peng, Y.C., Lin, C.L., Hsu, W.Y., Lu, I.T., Yeh, H.Z., Chang, C.-S., and Kao, C.H. (2018). Proton Pump Inhibitor Use is Associated with Risk of Pancreatic Cancer: A Nested Case\u2013Control Study. Dose-Response, 16.","DOI":"10.1177\/1559325818803283"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.3892\/ol.2020.11838","article-title":"The combination of orlistat, lonidamine and 6-diazo-5-oxo-L-norleucine induces a quiescent energetic phenotype and limits substrate flexibility in colon cancer cells","volume":"20","author":"Juarez","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/13543784.2018.1471132","article-title":"Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy","volume":"27","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, B.Y., Zhang, J., Wang, J.L., Sun, S., Wang, Z.H., Wang, L.P., Zhang, Q.L., Lv, F.F., Cao, E.Y., and Shao, Z.M. (2015). Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J. Exp. Clin. Cancer Res., 34.","DOI":"10.1186\/s13046-015-0194-x"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Esta\u00f1, M.C., Calvi\u00f1o, E., Calvo, S., Guill\u00e9n-Gu\u00edo, B., Boyano-Ad\u00e1nez, M.D.C., De Blas, E., Rial, E., and Aller, P. (2014). Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115250"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bbabio.2010.10.022","article-title":"Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells","volume":"1807","author":"Pike","year":"2011","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Loew, A., K\u00f6hnke, T., Rehbeil, E., Pietzner, A., and Weylandt, K.H. (2019). A Role for Lipid Mediators in Acute Myeloid Leukemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102425"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/neuonc\/now049","article-title":"Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma","volume":"18","author":"Cook","year":"2016","journal-title":"Neuro. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1053\/j.gastro.2015.07.064","article-title":"Prostaglandin E2 Promotes Colorectal Cancer Stem Cell Expansion and Metastasis in Mice","volume":"149","author":"Wang","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Finetti, F., Travelli, C., Ercoli, J., Colombo, G., Buoso, E., and Trabalzini, L. (2020). Prostaglandin E2 and cancer: Insight into tumor progression and immunity. Biology, 9.","DOI":"10.3390\/biology9120434"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, S., Svahn, S.L., and Johansson, M.E. (2019). Effects of omega-3 fatty acids on immune cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205028"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/MCO.0b013e32835d2d99","article-title":"Omega-3 fatty acids in cancer","volume":"16","author":"Laviano","year":"2013","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1096\/fj.201600611R","article-title":"Role of neutral ceramidase in colon cancer","volume":"30","author":"Coant","year":"2016","journal-title":"FASEB J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10555-011-9304-1","article-title":"Sphingolipids in cancer","volume":"30","author":"Furuya","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.2174\/1568026619666190227222930","article-title":"Acid Ceramidase: A Novel Therapeutic Target in Cancer","volume":"19","author":"Vijayan","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/carcin\/bgx097","article-title":"Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model","volume":"39","author":"Shimizu","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Furuya, H., Shimizu, Y., Tamashiro, P.M., Iino, K., Bielawski, J., Chan, O.T.M., Pagano, I., and Kawamori, T. (2017). Sphingosine kinase 1 expression enhances colon tumor growth. J. Transl. Med., 15.","DOI":"10.1186\/s12967-017-1220-x"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/carcin\/bgx104","article-title":"Sphingosine Kinase 1 expression in peritoneal macrophages is required for colon carcinogenesis","volume":"38","author":"Furuya","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12272-019-01114-3","article-title":"Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis","volume":"42","author":"Cho","year":"2019","journal-title":"Arch. Pharm. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.bbrc.2018.06.085","article-title":"Acid ceramidase inhibition sensitizes human colon cancer cells to oxaliplatin through downregulation of transglutaminase 2 and \u03b21 integrin\/FAK\u2212mediated signalling","volume":"503","author":"Visentin","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nrurol.2011.117","article-title":"Therapeutic potential of targeting sphingosine kinase 1 in prostate cancer","volume":"8","author":"Pchejetski","year":"2011","journal-title":"Nat. Rev. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"83208","DOI":"10.18632\/oncotarget.13079","article-title":"Acid ceramidase is upregulated in AML and represents a novel therapeutic target","volume":"7","author":"Tan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6915","DOI":"10.1158\/0008-5472.CAN-09-0664","article-title":"Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts","volume":"69","author":"Kapitonov","year":"2009","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/jn\/124.5.615","article-title":"Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice","volume":"124","author":"Dillehay","year":"1994","journal-title":"J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1093\/jn\/130.3.522","article-title":"Colonic cell proliferation and aberrant crypt foci formation are inhibited by dairy glycosphingolipids in 1,2-dimethylhydrazine-treated CF1 mice","volume":"130","author":"Schmelz","year":"2000","journal-title":"J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1158\/1078-0432.CCR-15-0126","article-title":"Molecular pathways: Fatty acid synthase","volume":"21","author":"Jones","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1158\/0008-5472.CAN-05-4673","article-title":"Fatty acid synthase and cancer: New application of an old pathway","volume":"66","author":"Kuhajda","year":"2006","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"De Oliveira, M.P., and Liesa, M. (2020). The Role of Mitochondrial Fat Oxidation in Cancer Cell Proliferation and Survival. Cells, 9.","DOI":"10.3390\/cells9122600"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1172\/JCI38942","article-title":"Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction","volume":"120","author":"Samudio","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cellsig.2017.06.017","article-title":"Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?","volume":"38","author":"Lee","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fung, M.K.L., and Chan, G.C.F. (2017). Drug-induced amino acid deprivation as strategy for cancer therapy. J. Hematol. Oncol., 10.","DOI":"10.1186\/s13045-017-0509-9"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/ng.3421","article-title":"NRF2 regulates serine biosynthesis in non-small cell lung cancer","volume":"47","author":"DeNicola","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Vi\u00e9, N., Copois, V., Bascoul-Mollevi, C., Denis, V., Bec, N., Robert, B., Fraslon, C., Conseiller, E., Molina, F., and Larroque, C. (2008). Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells. Mol. Cancer, 7.","DOI":"10.1186\/1476-4598-7-14"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.14336\/AD.2020.0314","article-title":"Serine and metabolism regulation: A novel mechanism in antitumor immunity and senescence","volume":"11","author":"Wu","year":"2020","journal-title":"Aging Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Choi, B.H., and Coloff, J.L. (2019). The diverse functions of non-essential amino acids in cancer. Cancers, 11.","DOI":"10.3390\/cancers11050675"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1085\/jgp.201812276","article-title":"Novel alanine serine cysteine transporter 2 (ASCT2) inhibitors based on sulfonamide and sulfonic acid ester scaffolds","volume":"151","author":"Ndaru","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Okazaki, K., Anzawa, H., Liu, Z., Ota, N., Kitamura, H., Onodera, Y., Alam, M.M., Matsumaru, D., Suzuki, T., and Katsuoka, F. (2020). Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-19593-0"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/nrc.2016.81","article-title":"Serine and one-carbon metabolism in cancer","volume":"16","author":"Yang","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Robertson, H., Dinkova-Kostova, A.T., and Hayes, J.D. (2020). Nrf2 and the ambiguous consequences of its activation during initiation and the subsequent stages of tumourigenesis. Cancers, 12.","DOI":"10.3390\/cancers12123609"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cmet.2016.12.011","article-title":"Serine Is an Essential Metabolite for Effector T Cell Expansion","volume":"25","author":"Ma","year":"2017","journal-title":"Cell Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature10350","article-title":"Functional genomics reveal that the serine synthesis pathway is essential in breast cancer","volume":"476","author":"Possemato","year":"2011","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1182\/blood.2019001034","article-title":"Amino acid metabolism in hematologic malignancies and the era of targeted therapy","volume":"134","author":"Tabe","year":"2019","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrc3557","article-title":"Serine, glycine and one-carbon units: Cancer metabolism in full circle","volume":"13","author":"Locasale","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nchembio.2070","article-title":"A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate","volume":"12","author":"Pacold","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1016\/j.celrep.2018.03.017","article-title":"Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism","volume":"22","author":"Gao","year":"2018","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.tem.2019.03.003","article-title":"Glutamine as an Essential Amino Acid for KRas-Driven Cancer Cells","volume":"30","author":"Bernfeld","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ejmech.2018.11.066","article-title":"Discovery and development of small molecule modulators targeting glutamine metabolism","volume":"163","author":"Li","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s43018-020-00160-x","article-title":"Targeting glutamine dependence through GLS1 inhibition suppresses ARID1A-inactivated clear cell ovarian carcinoma","volume":"2","author":"Wu","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_82","first-page":"4415","article-title":"Inhibition of the MYC-regulated glutaminase metabolic axis is an effective synthetic lethal approach for treating chemoresistant ovarian cancers","volume":"80","author":"Shen","year":"2021","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/13543776.2018.1530759","article-title":"Glutaminase inhibitors: A patent review","volume":"28","author":"Wu","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.chembiol.2006.10.010","article-title":"An Inhibitor of Human Asparagine Synthetase Suppresses Proliferation of an L-Asparaginase-Resistant Leukemia Cell Line","volume":"13","author":"Gutierrez","year":"2006","journal-title":"Chem. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.neo.2016.09.004","article-title":"Metabolic Alterations Caused by KRAS Mutations in Colorectal Cancer Contribute to Cell Adaptation to Glutamine Depletion by Upregulation of Asparagine Synthetase","volume":"18","author":"Toda","year":"2016","journal-title":"Neoplasia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm.4464","article-title":"Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models","volume":"24","author":"Schulte","year":"2018","journal-title":"Nat. Med."},{"key":"ref_87","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (2012). Asparaginase, National Institute of Diabetes and Digestive and Kidney Diseases."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nrc.2016.77","article-title":"Reprogramming glucose metabolism in cancer: Can it be exploited for cancer therapy?","volume":"16","author":"Hay","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Li, C.X., Sun, J.L., Gong, Z.C., Lin, Z.Q., and Liu, H. (2016). Prognostic value of GLUT-1 expression in oral squamous cell carcinoma A prisma-compliant meta-analysis. Medicine, 95.","DOI":"10.1097\/MD.0000000000005324"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.lungcan.2016.12.003","article-title":"Differential expression and prognostic significance of GLUT1 according to histologic type of non-small-cell lung cancer and its association with volume-dependent parameters","volume":"104","author":"Koh","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1002\/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X","article-title":"Overexpression of glut-1 glucose transporter in human breast cancer an immunohistochemical study","volume":"72","author":"Brown","year":"1993","journal-title":"Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1245\/s10434-018-6357-1","article-title":"Significance of Glucose Transporter Type 1 (GLUT-1) Expression in the Therapeutic Strategy for Pancreatic Ductal Adenocarcinoma","volume":"25","author":"Kurahara","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"24777","DOI":"10.18632\/oncotarget.15801","article-title":"STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1042\/bj0221289","article-title":"The carbohydrate metabolism of certain pathological overgrowths","volume":"22","author":"Crabtree","year":"1928","journal-title":"Biochem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1007\/s13277-015-4255-8","article-title":"Overexpression of Hexokinase 1 as a poor prognosticator in human colorectal cancer","volume":"37","author":"He","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"32332","DOI":"10.18632\/oncotarget.15974","article-title":"Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: A meta-analysis","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1158\/1541-7786.MCR-09-0234","article-title":"Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis","volume":"7","author":"Palmieri","year":"2009","journal-title":"Mol. Cancer Res."},{"key":"ref_98","first-page":"4054","article-title":"HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma","volume":"8","author":"Huang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.biocel.2017.12.010","article-title":"Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy","volume":"95","author":"Zhang","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1158\/0008-5472.CAN-11-0127","article-title":"Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism","volume":"71","author":"Zhao","year":"2011","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Deligiorgi, M.V., Liapi, C., and Trafalis, D.T. (2020). How far are we from prescribing fasting as anticancer medicine?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239175"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1126\/science.aat8515","article-title":"High-fructose corn syrup enhances intestinal tumor growth in mice","volume":"363","author":"Goncalves","year":"2019","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.copbio.2020.10.007","article-title":"Engineered diets to improve cancer outcomes","volume":"70","author":"Goncalves","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.yexcr.2016.11.002","article-title":"Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway","volume":"349","author":"Li","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.bbrc.2004.09.047","article-title":"Advanced cancers: Eradication in all cases using 3-bromopyruvate therapy to deplete ATP","volume":"324","author":"Ko","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.2147\/OTT.S243212","article-title":"Sinomenine inhibits non-small cell lung cancer via downregulation of hexokinases II-mediated aerobic glycolysis","volume":"13","author":"Liu","year":"2020","journal-title":"Onco. Targets. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s12013-014-0062-x","article-title":"Overexpression of MicroRNA-122 Re-sensitizes 5-FU-Resistant Colon Cancer Cells to 5-FU Through the Inhibition of PKM2 In Vitro and In Vivo","volume":"70","author":"He","year":"2014","journal-title":"Cell Biochem. Biophys."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3892\/ijmm.2012.989","article-title":"Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2","volume":"30","author":"Jiang","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Deng, Y., Li, X., Feng, J., and Zhang, X. (2018). Overexpression of miR-202 resensitizes imatinib resistant chronic myeloid leukemia cells through targetting Hexokinase 2. Biosci. Rep., 38.","DOI":"10.1042\/BSR20171383"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.1038\/s41388-018-0360-7","article-title":"Metformin sensitizes endometrial cancer cells to chemotherapy through IDH1-induced Nrf2 expression via an epigenetic mechanism","volume":"37","author":"Bai","year":"2018","journal-title":"Oncogene"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1177\/1933719111411731","article-title":"Dichloroacetate induces apoptosis of epithelial ovarian cancer cells through a mechanism involving modulation of oxidative stress","volume":"18","author":"Saed","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s13402-018-0398-0","article-title":"Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: Pivotal role of superoxide dismutase (SOD)","volume":"41","author":"Sharma","year":"2018","journal-title":"Cell. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Kitson, S.J., Rosser, M., Fischer, D.P., Marshall, K.M., Clarke, R.B., and Crosbie, E.J. (2019). Targeting endometrial cancer stem cell activity with metformin is inhibited by patient-derived adipocyte-secreted factors. Cancers, 11.","DOI":"10.1101\/562744"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s10147-020-01795-7","article-title":"Acid-suppressive agents and survival outcomes in patients with cancer: A systematic review and meta-analysis","volume":"26","author":"Song","year":"2021","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Koltai, T. (2020). Targeting the ph paradigm at the bedside: A practical approach. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239221"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Fais, S., and Marunaka, Y. (2020). The acidic microenvironment: Is it a phenotype of all cancers? a focus on multiple myeloma and some analogies with diabetes mellitus. Cancers, 12.","DOI":"10.3390\/cancers12113226"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Belisario, D.C., Kopecka, J., Pasino, M., Akman, M., De Smaele, E., Donadelli, M., and Riganti, C. (2020). Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance. Cells, 9.","DOI":"10.3390\/cells9122598"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Battello, N., Zimmer, A.D., Goebel, C., Dong, X., Behrmann, I., Haan, C., Hiller, K., and Wegner, A. (2016). The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells. Cancer Metab., 4.","DOI":"10.1186\/s40170-016-0141-0"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.3389\/fimmu.2019.01720","article-title":"NAD-Biosynthetic and Consuming Enzymes as Central Players of Metabolic Regulation of Innate and Adaptive Immune Responses in Cancer","volume":"10","author":"Audrito","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.semcdb.2019.05.001","article-title":"Targeting metabolic reprogramming in metastatic melanoma: The key role of nicotinamide phosphoribosyltransferase (NAMPT)","volume":"98","author":"Audrito","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"252","DOI":"10.15252\/embj.201695204","article-title":"Hypoxia-inducible factors: Coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype","volume":"36","author":"Semenza","year":"2017","journal-title":"EMBO J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/B978-0-12-416618-9.00022-4","article-title":"Analysis of hypoxia-induced metabolic reprogramming","volume":"Volume 542","author":"Yang","year":"2014","journal-title":"Methods in Enzymology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"209","DOI":"10.15430\/JCP.2016.21.4.209","article-title":"Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics","volume":"21","author":"Cha","year":"2016","journal-title":"J. Cancer Prev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/bjc.2016.149","article-title":"Statin use and all-cancer survival: Prospective results from the Women\u2019s Health Initiative","volume":"115","author":"Wang","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Chen, Y.A., Shih, H.W., Lin, Y.C., Hsu, H.Y., Wu, T.F., Tsai, C.H., Wu, C.L., Wu, H.Y., Hsieh, J.T., and Tang, C.H. (2018). Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00600"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Babcook, M.A., Sramkoski, R.M., Fujioka, H., Daneshgari, F., Almasan, A., Shukla, S., Nanavaty, R.R., and Gupta, S. (2014). Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells. Cell Death Dis., 5.","DOI":"10.1038\/cddis.2014.500"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/annonc\/mdy114","article-title":"Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: Current evidence and guidance for design of future trials","volume":"29","author":"Laviano","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s00726-016-2182-7","article-title":"Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid \u03b2-oxidation pathway in HepG2 cells","volume":"48","author":"Long","year":"2016","journal-title":"Amino Acids"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1194\/jlr.R061812","article-title":"Microtargeting cancer metabolism:Opening new therapeutic windows based on lipid metabolism","volume":"57","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.bbcan.2018.03.004","article-title":"Protein restriction and cancer","volume":"1869","author":"Yin","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature22056","article-title":"Modulating the therapeutic response of tumours to dietary serine and glycine starvation","volume":"544","author":"Maddocks","year":"2017","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Br\u00f6er, S. (2020). Amino acid transporters as targets for cancer therapy: Why, where, when, and how. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176156"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Yoshida, G.J. (2021). The harmonious interplay of amino acid andmonocarboxylate transporters induces the robustness of cancer cells. Metabolites, 11.","DOI":"10.3390\/metabo11010027"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1093\/advances\/nmaa062","article-title":"Perspective: Do Fasting, Caloric Restriction, and Diets Increase Sensitivity to Radiotherapy? A Literature Review","volume":"11","author":"Icard","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1136\/bmj.38415.708634.F7","article-title":"Metformin and reduced risk of cancer in diabetic patients","volume":"330","author":"Evans","year":"2005","journal-title":"Br. Med. J."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Poljsak, B., Kovac, V., Dahmane, R., Levec, T., and Starc, A. (2019). Cancer Etiology: A Metabolic Disease Originating from Life\u2019s Major Evolutionary Transition?. Oxid. Med. Cell. Longev., 2019.","DOI":"10.1155\/2019\/7831952"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1038\/onc.2016.391","article-title":"Metformin alters DNA methylation genome-wide via the H19\/SAHH axis","volume":"36","author":"Zhong","year":"2017","journal-title":"Oncogene"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrendo.2013.256","article-title":"Metformin-Mode of action and clinical implications for diabetes and cancer","volume":"10","author":"Pernicova","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Hu, L., Zeng, Z., Xia, Q., Liu, Z., Feng, X., Chen, J., Huang, M., Chen, L., Fang, Z., and Liu, Q. (2019). Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1\u03b1\/PFKFB3\/PFK1 pathway. Life Sci., 239.","DOI":"10.1016\/j.lfs.2019.116966"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13046-019-1211-2","article-title":"Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation","volume":"38","author":"Wang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1074\/jbc.M511064200","article-title":"Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited","volume":"281","author":"Schulz","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Yoo, J.J., Yu, S.J., Na, J., Kim, K., Cho, Y.Y., Lee, Y.B., Cho, E.J., Lee, J.H., Kim, Y.J., and Youn, H. (2019). Hexokinase-II inhibition synergistically augments the anti-tumor efficacy of sorafenib in hepatocellular carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061292"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"100","DOI":"10.18632\/genesandcancer.9","article-title":"Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells","volume":"5","author":"Zhang","year":"2014","journal-title":"Genes Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bbrc.2017.01.139","article-title":"Targeting hexokinase II as a possible therapy for cholangiocarcinoma","volume":"484","author":"Thamrongwaranggoon","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.gene.2017.10.046","article-title":"MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1","volume":"644","author":"Zhou","year":"2018","journal-title":"Gene"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2018.07.044","article-title":"Carbotoxicity\u2014Noxious Effects of Carbohydrates","volume":"175","author":"Kroemer","year":"2018","journal-title":"Cell"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Ludwig, D.S., Hu, F.B., Tappy, L., and Brand-Miller, J. (2018). Dietary carbohydrates: Role of quality and quantity in chronic disease. BMJ, 361.","DOI":"10.1136\/bmj.k2340"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Obrist, F., Michels, J., Durand, S., Chery, A., Pol, J., Levesque, S., Joseph, A., Astesana, V., Pietrocola, F., and Wu, G.S. (2018). Metabolic vulnerability of cisplatin-resistant cancers. EMBO J., 37.","DOI":"10.15252\/embj.201798597"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Kouidhi, S., Ayed, F.B., and Elgaaied, A.B. (2018). Targeting tumor metabolism: A new challenge to improve immunotherapy. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00353"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic Instruction of Immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Benavente, S., S\u00e1nchez-Garc\u00eda, A., Naches, S., LLeonart, M.E., and Lorente, J. (2020). Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.582884"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ejca.2016.02.020","article-title":"Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives","volume":"59","author":"Moehler","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Kim, S., Jang, J.Y., Koh, J., Kwon, D., Kim, Y.A., Paeng, J.C., Ock, C.Y., Keam, B., Kim, M., and Kim, T.M. (2019). Programmed cell death ligand-1-mediated enhancement of hexokinase 2 expression is inversely related to T-cell effector gene expression in non-small-cell lung cancer. J. Exp. Clin. Cancer Res., 38.","DOI":"10.1186\/s13046-019-1407-5"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Turbitt, W.J., Demark-Wahnefried, W., Peterson, C.M., and Norian, L.A. (2019). Targeting glucose metabolism to enhance immunotherapy: Emerging evidence on intermittent fasting and calorie restriction mimetics. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01402"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Daill\u00e8re, R., Derosa, L., Bonvalet, M., Segata, N., Routy, B., Gariboldi, M., Budinsk\u00e1, E., De Vries, I.J.M., Naccarati, A.G., and Zitvogel, V. (2020). Trial watch: The gut microbiota as a tool to boost the clinical efficacy of anticancer immunotherapy. Oncoimmunology, 9.","DOI":"10.1080\/2162402X.2020.1774298"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.62420","article-title":"The effects of age and systemic metabolism on anti-tumor t cell responses","volume":"9","author":"Drijvers","year":"2020","journal-title":"Elife"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.arr.2012.10.004","article-title":"Oxidative stress and cancer: An overview","volume":"12","author":"Sosa","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Ghoneum, A., Abdulfattah, A.Y., Warren, B.O., Shu, J., and Said, N. (2020). Redox homeostasis and metabolism in cancer: A complex mechanism and potential targeted therapeutics. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093100"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1073\/pnas.1700600114","article-title":"Metabolic origins of spatial organization in the tumor microenvironment","volume":"114","author":"Deforet","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Xiang, W., Shi, R., Zhang, D., Kang, X., Zhang, L., Yuan, J., Zhang, X., and Miao, H. (2020). Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4\/Cxcl10 axis in adipose tissue macrophages. Signal Transduct. Target. Ther., 5.","DOI":"10.1038\/s41392-020-00327-z"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e457","DOI":"10.1016\/S1470-2045(17)30411-4","article-title":"Physical activity, sedentary behaviour, diet, and cancer: An update and emerging new evidence","volume":"18","author":"Kerr","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"L\u00e9vesque, S., Pol, J.G., Ferrere, G., Galluzzi, L., Zitvogel, L., and Kroemer, G. (2019). Trial watch: Dietary interventions for cancer therapy. Oncoimmunology, 8.","DOI":"10.1080\/2162402X.2019.1591878"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.mcna.2017.06.004","article-title":"Diet, Physical Activity, and Body Weight in Cancer Survivorship","volume":"101","author":"Mehra","year":"2017","journal-title":"Med. Clin. N. Am."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1002\/cncr.24436","article-title":"Associations between lifestyle factors and quality of life among older long-term breast, prostate, and colorectal cancer survivors","volume":"115","author":"Mosher","year":"2009","journal-title":"Cancer"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1200\/JCO.2012.42.0638","article-title":"Lifestyle factors in cancer survivorship","volume":"30","author":"Ligibel","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jgo.2015.08.004","article-title":"Symptoms, weight loss, and physical function in a lifestyle intervention study of older cancer survivors","volume":"6","author":"Kenzik","year":"2015","journal-title":"J. Geriatr. Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Altea-Manzano, P., Cuadros, A.M., Broadfield, L.A., and Fendt, S. (2020). Nutrient metabolism and cancer in the in vivo context: A metabolic game of give and take. EMBO Rep., 21.","DOI":"10.15252\/embr.202050635"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Ibrahim, E.M., Al-Foheidi, M.H., and Al-Mansour, M.M. (2020). Energy and caloric restriction, and fasting and cancer: A narrative review. Support. Care Cancer.","DOI":"10.1007\/s00520-020-05879-y"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41568-019-0135-7","article-title":"Targeting cancer vulnerabilities with high-dose vitamin C","volume":"19","author":"Ngo","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Bhoora, S., and Punchoo, R. (2020). Policing cancer: Vitamin d arrests the cell cycle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239296"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1007\/s10620-018-4949-z","article-title":"Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats","volume":"63","author":"Walia","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.semcancer.2017.11.001","article-title":"Vitamin C\u2014A new player in regulation of the cancer epigenome","volume":"51","author":"Gillberg","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_173","first-page":"13985","article-title":"Nuclear cloning of embryonal carcinoma cells","volume":"101","author":"Blelloch","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.canlet.2019.07.010","article-title":"The tumour microenvironment as an integrated framework to understand cancer biology","volume":"461","author":"Lucantoni","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Sanegre, S., Lucantoni, F., Burgos-Panadero, R., de La Cruz-Merino, L., Noguera, R., and Naranjo, T.\u00c1. (2020). Integrating the tumor microenvironment into cancer therapy. Cancers, 12.","DOI":"10.3390\/cancers12061677"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.15252\/emmm.201707814","article-title":"Mutant CTNNB 1 and histological heterogeneity define metabolic subtypes of hepatoblastoma","volume":"9","author":"Crippa","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41388-020-01518-2","article-title":"Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma","volume":"40","author":"Nimmakayala","year":"2021","journal-title":"Oncogene"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/5\/264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:51Z","timestamp":1760161911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/5\/264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":177,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["metabo11050264"],"URL":"https:\/\/doi.org\/10.3390\/metabo11050264","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}