{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:08:00Z","timestamp":1784192880967,"version":"3.55.0"},"reference-count":108,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Metabolic reprogramming is a unifying characteristic of cancer and involves orchestrated changes in glucose, amino acid, lipid, and mitochondrial metabolism that go beyond the well-known Warburg effect. Evidence is accumulating that these metabolic states are actively remodeled by oncogene signaling and tumor suppressor loss, allowing cancer cells to sustain anabolic growth, redox homeostasis, and therapeutic stress. This review provides an overview of new findings on tumor metabolism, mechanisms, and the molecular networks governing this reprogramming. We discuss how the major oncogenic pathways, such as MYC, mTOR, HIF, and AMPK, reprogram metabolism using transcriptional, epigenetic, and post-translational control of metabolic flux. A focus is placed on mitochondrial bioenergetics, dynamics, and metabolite signaling such as cancer cell fitness and stress tolerance-defining factors. We also discussed metabolic crosstalk in the tumor ecosystem, including nutrient competition, metabolite coupling, and immunometabolic reprogramming to coordinate metabolism-mediated effects on tumorigenesis and therapeutic response. The review further considers the mechanistic basis for metabolism-targeted therapies, including pathway dependencies, adaptive responses, and micro-environmental context that constrain clinical benefit. Recent innovations such as spatial metabolomics, single-cell metabolic profiling, and systems-level models have unveiled significant intratumoral heterogeneity of metabolism, and they have provided important information about diverse vulnerabilities to therapeutic intervention. Accordingly, understanding the complex crosstalk between these metabolic networks is crucial to rationally designing combination strategies that selectively leverage cancer-specific metabolic liabilities with minimal toxicities against normal tissues.<\/jats:p>","DOI":"10.3390\/cimb48070723","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumoral Metabolism at the Intersection of Oncogene Signaling, Epigenetics and Immunology: Emerging Therapeutic Strategies in Cancer"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-7125","authenticated-orcid":false,"given":"Bhoomendra A.","family":"Bhongade","sequence":"first","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-7665","authenticated-orcid":false,"given":"Areeg Anwer","family":"Ali","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakta Mani","family":"Satyam","sequence":"additional","affiliation":[{"name":"RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-2332","authenticated-orcid":false,"given":"Sirajunisa","family":"Talath","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-2820","authenticated-orcid":false,"given":"Adil Farooq","family":"Wali","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-8158","authenticated-orcid":false,"given":"Syed Arman","family":"Rabbani","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa","family":"Ibraheem","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-4094","authenticated-orcid":false,"given":"Karolina","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashot","family":"Avagimyan","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases Propedeutics, Yerevan State Medical University After M. Heratsi, Yerevan 0025, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7441","authenticated-orcid":false,"given":"Ioannis","family":"Ilias","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, GR-11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3401-1232","authenticated-orcid":false,"given":"Sorina","family":"Ispas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of General Medicine, \u201cOvidius\u201d University, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Maggio","sequence":"additional","affiliation":[{"name":"School of Medicine, PROMISE Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medicinal Specialties, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-2632","authenticated-orcid":false,"given":"Anna","family":"Paczkowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"},{"name":"School of Medicine, PROMISE Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medicinal Specialties, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","article-title":"The metabolism of tumors in the body","volume":"8","author":"Warburg","year":"1927","journal-title":"J. Gen. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.cell.2018.03.055","article-title":"Metabolomics and isotope tracing","volume":"173","author":"Jang","year":"2018","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1002\/mco2.218","article-title":"Metabolic reprogramming in cancer: Mechanisms and therapeutics","volume":"4","author":"Nong","year":"2023","journal-title":"MedComm"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111239","DOI":"10.1016\/j.cellsig.2024.111239","article-title":"Exploring the mystery of tumor metabolism: Warburg effect and mitochondrial metabolism fighting side by side","volume":"120","author":"Yu","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aaf4405","article-title":"Hypoxic control of metastasis","volume":"352","author":"Rankin","year":"2016","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature15726","article-title":"Oxidative stress inhibits distant metastasis by human melanoma cells","volume":"527","author":"Piskounova","year":"2015","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15965","DOI":"10.1038\/ncomms15965","article-title":"Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism","volume":"8","author":"Biancur","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_9","first-page":"130301","article-title":"Metabolic reprograming of cancer as a therapeutic target","volume":"1866","author":"Furukawa","year":"2022","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.cell.2015.12.034","article-title":"Metabolic heterogeneity in human lung tumors","volume":"164","author":"Hensley","year":"2016","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1158\/2159-8290.CD-19-0292","article-title":"Targeting autophagy in cancer: Recent advances and future directions","volume":"9","author":"Amaravadi","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.cell.2017.09.019","article-title":"Lactate metabolism in human lung tumors","volume":"171","author":"Faubert","year":"2017","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1038\/s41591-018-0052-4","article-title":"An inhibitor of oxidative phosphorylation exploits cancer vulnerability","volume":"24","author":"Molina","year":"2018","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm.4464","article-title":"Pharmacological blockade of ASCT2 dependent glutamine transport leads to antitumour efficacy in preclinical models","volume":"24","author":"Schulte","year":"2018","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3892\/ol.2023.13745","article-title":"Role and therapeutic targeting of glutamine metabolism in non-small cell lung cancer","volume":"25","author":"Zhou","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nature17393","article-title":"Reductive carboxylation supports redox homeostasis during anchorage independent growth","volume":"532","author":"Jiang","year":"2016","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nature08617","article-title":"Cancer-associated IDH1 mutations produce 2-hydroxyglutarate","volume":"462","author":"Dang","year":"2009","journal-title":"Nature"},{"key":"ref_18","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_19","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_20","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature25465","article-title":"Asparagine bioavailability governs metastasis in a model of breast cancer","volume":"554","author":"Knott","year":"2018","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/jamaoncol.2016.3049","article-title":"Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: A randomized clinical trial","volume":"3","author":"Szlosarek","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-019-1437-3","article-title":"Dietary methionine influences therapy in mouse cancer models and alters human metabolism","volume":"572","author":"Gao","year":"2019","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.ebiom.2015.06.020","article-title":"Inhibition of de novo palmitate synthesis by fatty acid synthase induces apoptosis in tumour cells by remodeling cell membranes, inhibiting signalling pathways, and reprogramming gene expression","volume":"2","author":"Ventura","year":"2015","journal-title":"eBioMedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nm.4181","article-title":"Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models","volume":"22","author":"Svensson","year":"2016","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1158\/0008-5472.CAN-19-0369","article-title":"Stearoyl CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death","volume":"79","author":"Tesfay","year":"2019","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1158\/1535-7163.MCT-14-0183","article-title":"Lipid catabolism via CPT1 as a therapeutic target for prostate cancer","volume":"13","author":"Schlaepfer","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1182\/blood-2014-12-617498","article-title":"Targeting the leukemia cell metabolism by the CPT1a inhibition: Functional preclinical effects in leukemias","volume":"126","author":"Ricciardi","year":"2015","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100797","DOI":"10.1016\/j.eclinm.2021.100797","article-title":"First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors","volume":"34","author":"Falchook","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molcel.2015.12.014","article-title":"Serine metabolism supports the methionine cycle and DNA\/RNA methylation through de novo ATP synthesis in cancer cells","volume":"61","author":"Maddocks","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1073\/pnas.1521548113","article-title":"Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers","volume":"113","author":"Mullarky","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.cmet.2016.04.016","article-title":"Reversal of cytosolic one carbon flux compensates for loss of the mitochondrial folate pathway","volume":"23","author":"Ducker","year":"2016","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.chembiol.2016.11.013","article-title":"Rational design of selective allosteric inhibitors of PHGDH and serine synthesis with anti-tumor activity","volume":"24","author":"Wang","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cmet.2016.01.007","article-title":"Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer","volume":"23","author":"Davidson","year":"2016","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1056\/NEJMoa1716984","article-title":"Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML","volume":"378","author":"DiNardo","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.bbrc.2018.06.049","article-title":"The anti-malarial atovaquone selectively increases chemosensitivity in retinoblastoma via mitochondrial dysfunction-dependent oxidative damage and Akt\/AMPK\/mTOR inhibition","volume":"504","author":"Ke","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nature19084","article-title":"Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion","volume":"536","author":"Sousa","year":"2016","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature19795","article-title":"On-target efficacy of a HIF-2\u03b1 antagonist in preclinical kidney cancer models","volume":"539","author":"Cho","year":"2016","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1021\/acs.biochem.5b00375","article-title":"Lysine acetylation activates mitochondrial aconitase in the heart","volume":"54","author":"Fernandes","year":"2015","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/nm.4399","article-title":"Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells","volume":"23","author":"Kuntz","year":"2017","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nm.4055","article-title":"Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer","volume":"22","author":"Camarda","year":"2016","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/onc.2015.179","article-title":"Oncogenic PI3K and KRAS stimulate de novo lipid synthesis through mTORC1 and SREBP","volume":"35","author":"Ricoult","year":"2016","journal-title":"Oncogene"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1038\/nm.4407","article-title":"KEAP1 loss promotes KRAS-driven lung cancer and results in dependence on glutaminolysis","volume":"23","author":"Romero","year":"2017","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signalling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/abbs\/gmt144","article-title":"Tumor suppressor p53 and its gain-of-function mutants in cancer","volume":"46","author":"Liu","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_45","first-page":"6109","article-title":"Mitochondrial lysine deacetylation promotes energy metabolism and calcium signaling in insulin-secreting cells","volume":"33","author":"Thevenet","year":"2019","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"44376","DOI":"10.1074\/jbc.M205911200","article-title":"Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication","volume":"277","author":"Angus","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/cdd.2014.139","article-title":"AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62\/SQSTM1","volume":"22","author":"Strappazzon","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nature19353","article-title":"Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition","volume":"537","author":"Sciacovelli","year":"2016","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1126\/science.1164097","article-title":"ATP-citrate lyase links cellular metabolism to histone acetylation","volume":"324","author":"Wellen","year":"2009","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmet.2014.06.004","article-title":"Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation","volume":"20","author":"Lee","year":"2014","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S1470-2045(21)00494-0","article-title":"Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant IDH2 acute myeloid leukaemia (AG221-AML-005): A single-arm, phase 1b and randomized, phase 2 trial","volume":"22","author":"DiNardo","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/j.ajpath.2013.01.048","article-title":"Inhibition of ATP citrate lyase induces an anticancer effect via reactive oxygen species: AMPK as a predictive biomarker for therapeutic impact","volume":"182","author":"Migita","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1139\/apnm-2020-0005","article-title":"PGC-1\u03b1-mediated regulation of mitochondrial function and physiological implications","volume":"45","author":"Halling","year":"2020","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e6019","DOI":"10.7554\/eLife.60191","article-title":"MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor-1","volume":"10","author":"Popay","year":"2021","journal-title":"eLife"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2015.11.002","article-title":"Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy","volume":"23","author":"Sukumar","year":"2016","journal-title":"Cell Metab."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hu, C., Huang, Y., and Li, L. (2017). Drp1-dependent mitochondrial fission plays critical roles in physiological and pathological processes in mammals. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010144"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.molcel.2015.01.002","article-title":"Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth","volume":"57","author":"Kashatus","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8472","DOI":"10.1038\/ncomms9472","article-title":"Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs","volume":"6","author":"Phinney","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9073","DOI":"10.1038\/srep09073","article-title":"MitoCeption as a new tool to assess the effects of mesenchymal stem\/stromal cell mitochondria on cancer cell metabolism and function","volume":"5","author":"Caicedo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e22187","DOI":"10.7554\/eLife.22187","article-title":"Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells","volume":"6","author":"Dong","year":"2017","journal-title":"eLife"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cmet.2014.12.003","article-title":"Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA","volume":"21","author":"Tan","year":"2015","journal-title":"Cell Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1038\/s41388-019-0805-7","article-title":"Cancer-associated fibroblasts promote prostate cancer malignancy via metabolic rewiring and mitochondrial transfer","volume":"38","author":"Ippolito","year":"2019","journal-title":"Oncogene"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1479-5876-11-94","article-title":"Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance","volume":"11","author":"Pasquier","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e02935","DOI":"10.7554\/eLife.02935","article-title":"Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer","volume":"3","author":"Ju","year":"2014","journal-title":"eLife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e10769","DOI":"10.7554\/eLife.10769","article-title":"Mitochondrial DNA copy number variation across human cancers","volume":"5","author":"Reznik","year":"2016","journal-title":"eLife"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41392-025-02311-x","article-title":"Mitochondrial metabolism and cancer therapeutic innovation","volume":"10","author":"Du","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16028","DOI":"10.1073\/pnas.1906896116","article-title":"Regulation of nuclear epigenome by mitochondrial DNA heteroplasmy","volume":"116","author":"Kopinski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s12276-024-01180-8","article-title":"Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer","volume":"56","author":"Bae","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41586-021-03442-1","article-title":"Cell-programmed nutrient partitioning in the tumour microenvironment","volume":"593","author":"Reinfeld","year":"2021","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic competition in the tumor microenvironment is a driver of cancer progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1126\/science.aav2588","article-title":"Glutamine blockade induces divergent metabolic programmes to overcome tumour immune evasion","volume":"366","author":"Leone","year":"2019","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Haas, R., Smith, J., Rocher-Ros, V., Nadkarni, S., Montero-Melendez, T., D\u2019Acquisto, F., Bland, E.J., Bombardieri, M., Pitzalis, C., and Perretti, M. (2015). Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol., 13.","DOI":"10.1371\/journal.pbio.1002202"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3324\/haematol.2016.163030","article-title":"Inhibition of monocarboxylate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma","volume":"102","author":"Noble","year":"2017","journal-title":"Haematologica"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69219","DOI":"10.18632\/oncotarget.18215","article-title":"Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL and Burkitt\u2019s lymphoma anti-tumor activity","volume":"8","author":"Curtis","year":"2017","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1470-2045(19)30274-8","article-title":"Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301\/KEYNOTE-252): A phase 3, randomised, double-blind study","volume":"20","author":"Long","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e1208875","DOI":"10.1080\/2162402X.2016.1208875","article-title":"Targeting CD73 in the tumor microenvironment with MEDI9447","volume":"5","author":"Hay","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1200\/JCO.2017.35.15_suppl.3005","article-title":"A first-in-human phase 1 study of CB-1158, a small molecule inhibitor of arginase, as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients (pts) with solid tumors","volume":"35","author":"Papadopoulos","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s42003-018-0178-4","article-title":"Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction","volume":"1","author":"Cheng","year":"2018","journal-title":"Commun. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1172\/JCI131859","article-title":"Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells","volume":"130","author":"Oh","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9464","DOI":"10.1038\/s41467-024-53706-3","article-title":"Prostaglandin E2-EP2\/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells","volume":"15","author":"Punyawatthananukool","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.cell.2015.08.015","article-title":"Cyclooxygenase-dependent tumor growth through evasion of immunity","volume":"162","author":"Zelenay","year":"2015","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/s41419-020-03175-5","article-title":"Cancer cell metabolic reprogramming: A keystone for the response to immunotherapy","volume":"11","author":"Cerezo","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1172\/JCI76012","article-title":"Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation","volume":"125","author":"Gerriets","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cmet.2016.12.018","article-title":"Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments","volume":"25","author":"Angelin","year":"2017","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.cmet.2018.02.024","article-title":"Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy","volume":"27","author":"Cascone","year":"2018","journal-title":"Cell Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1158\/2326-6066.CIR-16-0103","article-title":"Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia","volume":"5","author":"Scharping","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"40621","DOI":"10.18632\/oncotarget.9746","article-title":"Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1073\/pnas.0914433107","article-title":"Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression","volume":"107","author":"Le","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1002\/cmdc.201600276","article-title":"Identification and optimization of the first highly selective GLUT1 inhibitor BAY-876","volume":"11","author":"Siebeneicher","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_94","first-page":"552","article-title":"CB-839, a selective glutaminase inhibitor, has anti-tumour activity in renal cell carcinoma and synergises with cabozantinib and everolimus","volume":"76","author":"Emberley","year":"2016","journal-title":"Proc. Am. Assoc. Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.clon.2019.05.023","article-title":"CB-839, a glutaminase inhibitor, in combination with cabozantinib in patients with clear cell and papillary metastatic renal cell cancer (mRCC): Results of a phase I study","volume":"37","author":"Lee","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E5328","DOI":"10.1073\/pnas.1611406113","article-title":"Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer","volume":"113","author":"Elgogary","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.cmet.2021.02.001","article-title":"Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth","volume":"33","author":"Krall","year":"2021","journal-title":"Cell Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ebiom.2016.12.012","article-title":"FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression","volume":"16","author":"Heuer","year":"2017","journal-title":"eBioMedicine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cmet.2018.08.020","article-title":"Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma","volume":"29","author":"Lally","year":"2019","journal-title":"Cell Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumour suppression","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ccell.2014.12.002","article-title":"Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress","volume":"27","author":"Schug","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature13110","article-title":"Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides","volume":"508","author":"Birsoy","year":"2014","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41591-022-02103-8","article-title":"Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: Phase I trials","volume":"29","author":"Yap","year":"2023","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"34084","DOI":"10.18632\/oncotarget.9122","article-title":"Repurposing atovaquone: Targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells","volume":"7","author":"Fiorillo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1172\/JCI78239","article-title":"Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment","volume":"125","author":"Tanaka","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"817","DOI":"10.15252\/msb.20145307","article-title":"Modeling cancer metabolism on a genome scale","volume":"11","author":"Yizhak","year":"2015","journal-title":"Mol. Syst. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1016\/j.cgh.2018.04.042","article-title":"Acetyl-CoA carboxylase inhibitor GS-0976 for 12 weeks reduces hepatic de novo lipogenesis and steatosis in patients with nonalcoholic steatohepatitis","volume":"16","author":"Lawitz","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.celrep.2016.03.043","article-title":"MTAP deletions in cancer create vulnerability to targeting of the MAT2A\/PRMT5\/RIOK1 axis","volume":"15","author":"Marjon","year":"2016","journal-title":"Cell Rep."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/723\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:00:59Z","timestamp":1784192459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":108,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070723"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070723","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]}}}