{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:12:55Z","timestamp":1788502375091,"version":"build-2803163510"},"reference-count":335,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","award":["1460028"],"award-info":[{"award-number":["1460028"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Metabolic reprogramming is a defining feature of breast cancer, enabling tumor cells to sustain rapid proliferation, survive under stress, and resist therapy. Key pathways including glycolysis, glutaminolysis, lipid metabolism, and one-carbon metabolism, play central roles in meeting the energetic and biosynthetic demands of malignant cells. Enhanced glycolytic flux supports ATP generation and lactate production, while glutamine metabolism fuels the tricarboxylic acid cycle and provides nitrogen for nucleotide synthesis. Lipid metabolic pathways, particularly fatty acid synthesis, contribute to membrane biogenesis and signaling, and one-carbon metabolism driven by serine and glycine supplies methyl groups for epigenetic regulation and nucleotide production. These metabolic adaptations not only promote tumor growth but also create vulnerabilities that can be exploited therapeutically. Inhibiting these pathways has shown promise in preclinical models; however, challenges such as metabolic plasticity, tumor heterogeneity, and potential toxicity in normal tissues underscore the need for biomarker-driven strategies and rational combination therapies. Herein, we describe current knowledge of the role of these pathways in breast cancer progression, highlighting the role of key enzymes in promoting breast cancer tumor cell growth and in breast cancer prognoses.<\/jats:p>","DOI":"10.3390\/curroncol33020129","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T11:39:10Z","timestamp":1771846750000},"page":"129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7879-4280","authenticated-orcid":false,"given":"Sabrina","family":"Guo","sequence":"first","affiliation":[{"name":"Cancer Research Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-475X","authenticated-orcid":false,"given":"Christina L.","family":"Addison","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8L1, Canada"},{"name":"Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9S","DOI":"10.2967\/jnumed.115.157834","article-title":"Clinical Diagnosis and Management of Breast Cancer","volume":"57","author":"McDonald","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.4161\/cc.22776","article-title":"BRCA1 mutations drive oxidative stress and glycolysis in the tumor microenvironment","volume":"11","author":"Balliet","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40170-018-0175-6","article-title":"Metabolomics of oncogene-specific metabolic reprogramming during breast cancer","volume":"6","author":"Dai","year":"2018","journal-title":"Cancer Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E7697","DOI":"10.1073\/pnas.1710366114","article-title":"Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC","volume":"114","author":"Satoh","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gandhi, N., and Das, G.M. (2019). Metabolic Reprogramming in Breast Cancer and Its Therapeutic Implications. Cells, 8.","DOI":"10.3390\/cells8020089"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10684","DOI":"10.1073\/pnas.1411026111","article-title":"Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion","volume":"111","author":"Zhang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ncb2172","article-title":"p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase","volume":"13","author":"Jiang","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12964-023-01449-x","article-title":"Glutamine addiction in tumor cell: Oncogene regulation and clinical treatment","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/BST0350305","article-title":"Metabolic enzymes regulated by the Myc oncogene are possible targets for chemotherapy or chemoprevention","volume":"35","author":"Rimpi","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e70120","DOI":"10.1002\/mco2.70120","article-title":"Glutamine Metabolism: Molecular Regulation, Biological Functions, and Diseases","volume":"6","author":"Kumar","year":"2025","journal-title":"Medcomm"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pupo, E., Avanzato, D., Middonti, E., Bussolino, F., and Lanzetti, L. (2019). KRAS-Driven Metabolic Rewiring Reveals Novel Actionable Targets in Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00848"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ni, R., Li, Z., Li, L., Peng, D., Ming, Y., Li, L., and Liu, Y. (2023). Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1143798"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Muranaka, H., Akinsola, R., Billet, S., Pandol, S.J., Hendifar, A.E., Bhowmick, N.A., and Gong, J. (2024). Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention. Cancers, 16.","DOI":"10.3390\/cancers16051057"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.1038\/s41467-023-42458-1","article-title":"Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth","volume":"14","author":"Tombari","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/cr.2015.33","article-title":"cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions","volume":"25","author":"Sun","year":"2015","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3892\/ijo.2020.5158","article-title":"Serine, glycine and one-carbon metabolism in cancer (Review)","volume":"58","author":"Pan","year":"2020","journal-title":"Int. J. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/nature20132","article-title":"LKB1 loss links serine metabolism to DNA methylation and tumorigenesis","volume":"539","author":"Kottakis","year":"2016","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.advnut.2023.05.007","article-title":"Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment","volume":"14","author":"Shunxi","year":"2023","journal-title":"Adv. Nutr. Int. Rev. J."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lei, P., Wang, W., Sheldon, M., Sun, Y., Yao, F., and Ma, L. (2023). Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance. Cancers, 15.","DOI":"10.3390\/cancers15133390"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.tem.2021.07.001","article-title":"Integrating metabolic reprogramming and metabolic imaging to predict breast cancer therapeutic responses","volume":"32","author":"Liu","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sun, X., Wang, M., Wang, M., Yu, X., Guo, J., Sun, T., Li, X., Yao, L., Dong, H., and Xu, Y. (2020). Metabolic Reprogramming in Triple-Negative Breast Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00428"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.1007\/s11033-021-06414-w","article-title":"Metabolic changes in triple negative breast cancer-focus on aerobic glycolysis","volume":"48","author":"Arundhathi","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29487","DOI":"10.18632\/oncotarget.15494","article-title":"Fatty acid metabolism in breast cancer subtypes","volume":"8","author":"Monaco","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a040535","DOI":"10.1101\/cshperspect.a040535","article-title":"Glycolysis","volume":"13","author":"Chandel","year":"2021","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12967-020-02267-2","article-title":"Comprehensive analysis of the association between tumor glycolysis and immune\/inflammation function in breast cancer","volume":"18","author":"Li","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1515\/biol-2018-0068","article-title":"Up-regulation of key glycolysis proteins in cancer development","volume":"13","author":"Nowak","year":"2018","journal-title":"Open Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.18632\/oncotarget.2766","article-title":"Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells","volume":"6","author":"Shiraishi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"105190","DOI":"10.1016\/j.isci.2022.105190","article-title":"Link between glucose metabolism and epithelial-to-mesenchymal transition drives triple-negative breast cancer migratory heterogeneity","volume":"25","author":"Schwager","year":"2022","journal-title":"iScience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1080\/01635581.2019.1654527","article-title":"Higher Glucose Enhances Breast Cancer Cell Aggressiveness","volume":"72","author":"Santos","year":"2019","journal-title":"Nutr. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.20892\/j.issn.2095-3941.2019.0210","article-title":"Metabolic reprogramming in triple-negative breast cancer","volume":"17","author":"Wang","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/0008-5472.CAN-15-2478","article-title":"EGFR Signaling Enhances Aerobic Glycolysis in Triple-Negative Breast Cancer Cells to Promote Tumor Growth and Immune Escape","volume":"76","author":"Lim","year":"2016","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108168","DOI":"10.1016\/j.isci.2023.108168","article-title":"MUC1-C integrates aerobic glycolysis with suppression of oxidative phosphorylation in triple-negative breast cancer stem cells","volume":"26","author":"Yamashita","year":"2023","journal-title":"iScience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1111\/cas.12238","article-title":"Hexokinase II in breast carcinoma: A potent prognostic factor associated with hypoxia-inducible factor-1\u03b1 and Ki-67","volume":"104","author":"Suzuki","year":"2013","journal-title":"Cancer Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0969-8051(02)00288-3","article-title":"Expression of hexokinase II and Glut-1 in untreated human breast cancer","volume":"29","author":"Brown","year":"2002","journal-title":"Nucl. Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18807","DOI":"10.1038\/s41598-022-23598-8","article-title":"A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors","volume":"12","author":"Li","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.ajpath.2021.12.006","article-title":"SETD5 Regulates Glycolysis in Breast Cancer Stem-Like Cells and Fuels Tumor Growth","volume":"192","author":"Yang","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1038\/emboj.2012.45","article-title":"A novel miR-155\/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells","volume":"31","author":"Jiang","year":"2012","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ccell.2017.10.003","article-title":"An HIF-1\u03b1\/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression","volume":"32","author":"Palazon","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000217529","article-title":"Glycolytic Enzymes in Breast Cancer, Benign Breast Disease and Normal Breast Tissue","volume":"8","author":"Hennipman","year":"1987","journal-title":"Tumor Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.7150\/ijbs.48933","article-title":"MicroRNA-216b targets HK2 to potentiate autophagy and apoptosis of breast cancer cells via the mTOR signaling pathway","volume":"17","author":"Liu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","unstructured":"Ishfaq, M., Bashir, N., Riaz, S.K., Manzoor, S., Khan, J.S., Bibi, Y., Sami, R., Aljahani, A.H., Alharthy, S.A., and Shahid, R. (2022). Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients. Genes, 13.","DOI":"10.3390\/genes13030549"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1038\/onc.2016.150","article-title":"A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer","volume":"35","author":"Ma","year":"2016","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7381","DOI":"10.1128\/MCB.00440-07","article-title":"Hypoxia-Inducible Factor 1 and Dysregulated c-Myc Cooperatively Induce Vascular Endothelial Growth Factor and Metabolic Switches Hexokinase 2 and Pyruvate Dehydrogenase Kinase 1","volume":"27","author":"Kim","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1158\/1940-6207.CAPR-16-0281","article-title":"Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention","volume":"10","author":"Chiyoda","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12032-023-02008-7","article-title":"ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion","volume":"40","author":"Ma","year":"2023","journal-title":"Med Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Foster, R., Griffin, S., Grooby, S., Feltell, R., Christopherson, C., Chang, M., Sninsky, J., Kwok, S., and Torrance, C. (2012). Multiple Metabolic Alterations Exist in Mutant PI3K Cancers, but Only Glucose Is Essential as a Nutrient Source. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045061"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12935-016-0280-y","article-title":"Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth","volume":"16","author":"Wang","year":"2016","journal-title":"Cancer Cell Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ccr.2013.06.014","article-title":"Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer","volume":"24","author":"Patra","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"290","DOI":"10.21037\/tcr.2019.01.37","article-title":"Downregulation of hexokinase 2 improves radiosensitivity of breast cancer","volume":"8","author":"Zhang","year":"2019","journal-title":"Transl. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8464","DOI":"10.1021\/acs.jmedchem.3c00118","article-title":"Degradation of Hexokinase 2 Blocks Glycolysis and Induces GSDME-Dependent Pyroptosis to Amplify Immunogenic Cell Death for Breast Cancer Therapy","volume":"66","author":"Sang","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/s12672-025-02320-w","article-title":"Inhibiting glycolysis facilitated checkpoint blockade therapy for triple-negative breast cancer","volume":"16","author":"Li","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41420-023-01412-2","article-title":"Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis","volume":"9","author":"Li","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e23827","DOI":"10.1016\/j.heliyon.2023.e23827","article-title":"Long non-coding RNA HANR modulates the glucose metabolism of triple negative breast cancer via stabilizing hexokinase 2","volume":"10","author":"Han","year":"2023","journal-title":"Heliyon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e383","DOI":"10.1038\/oncsis.2017.83","article-title":"TNF\u03b1-YAP\/p65-HK2 axis mediates breast cancer cell migration","volume":"6","author":"Gao","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-28440-3","article-title":"A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis","volume":"13","author":"Blaha","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1038\/s41467-019-10374-y","article-title":"Non-proteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion","volume":"10","author":"Lee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.molcel.2004.11.014","article-title":"Hexokinase-Mitochondria Interaction Mediated by Akt Is Required to Inhibit Apoptosis in the Presence or Absence of Bax and Bak","volume":"16","author":"Majewski","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e000355","DOI":"10.1161\/JAHA.113.000355","article-title":"Cardiac-specific Hexokinase 2 Overexpression Attenuates Hypertrophy by Increasing Pentose Phosphate Pathway Flux","volume":"2","author":"McCommis","year":"2013","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1128\/MCB.00224-07","article-title":"Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II","volume":"28","author":"Sun","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"L573","DOI":"10.1152\/ajplung.00410.2001","article-title":"Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury","volume":"283","author":"Ahmad","year":"2002","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1128\/MCB.23.20.7315-7328.2003","article-title":"Akt-Directed Glucose Metabolism Can Prevent Bax Conformation Change and Promote Growth Factor-Independent Survival","volume":"23","author":"Rathmell","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7610","DOI":"10.1074\/jbc.M109950200","article-title":"Mitochondrial Binding of Hexokinase II Inhibits Bax-induced Cytochrome c Release and Apoptosis","volume":"277","author":"Pastorino","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.molcel.2013.12.019","article-title":"Hexokinase-II Positively Regulates Glucose Starvation-Induced Autophagy through TORC1 Inhibition","volume":"53","author":"Roberts","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lin, J., Fang, W., Xiang, Z., Wang, Q., Cheng, H., Chen, S., Fang, J., Liu, J., Wang, Q., and Lu, Z. (2023). Glycolytic enzyme HK2 promotes PD-L1 expression and breast cancer cell immune evasion. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1189953"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1186\/s13046-019-1407-5","article-title":"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","volume":"38","author":"Kim","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1038\/s41388-018-0386-x","article-title":"PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer","volume":"37","author":"Yang","year":"2018","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1074\/mcp.RA119.001576","article-title":"Elevated Hexokinase II Expression Confers Acquired Resistance to 4-Hydroxytamoxifen in Breast Cancer Cells","volume":"18","author":"Liu","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/s41419-023-06009-2","article-title":"Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2","volume":"14","author":"Zheng","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1186\/s12935-020-01514-2","article-title":"Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells","volume":"20","author":"Hamzah","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/sj.bjc.6600547","article-title":"Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell death","volume":"87","author":"Aft","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4048\/jbc.2012.15.2.141","article-title":"Enhanced Radiosensitivity and Chemosensitivity of Breast Cancer Cells by 2-Deoxy-D-Glucose in Combination Therapy","volume":"15","author":"Aghaee","year":"2012","journal-title":"J. Breast Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41420-022-01074-6","article-title":"The combination of hydroxychloroquine and 2-deoxyglucose enhances apoptosis in breast cancer cells by blocking protective autophagy and sustaining endoplasmic reticulum stress","volume":"8","author":"Zhou","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1158\/0008-5472.CAN-11-3928","article-title":"Mitochondria-Targeted Drugs Synergize with 2-Deoxyglucose to Trigger Breast Cancer Cell Death","volume":"72","author":"Cheng","year":"2012","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.21873\/anticanres.11185","article-title":"Enhancing the Therapeutic Efficacy of 2-Deoxyglucose in Breast Cancer Cells Using Cell-cycle Synchronization","volume":"36","author":"Lee","year":"2016","journal-title":"Anticancer. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.3892\/or.2017.5491","article-title":"Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors","volume":"37","author":"Wokoun","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Repas, J., Zupin, M., Vodlan, M., Verani\u010d, P., Gole, B., Poto\u010dnik, U., and Pavlin, M. (2022). Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells. Cancers, 14.","DOI":"10.3390\/cancers14051343"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0304-3835(01)00667-X","article-title":"Glucose catabolism in the rabbit VX2 tumor model for liver cancer: Characterization and targeting hexokinase","volume":"173","author":"Ko","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13046-017-0530-4","article-title":"Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2","volume":"36","author":"Li","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"105367","DOI":"10.1016\/j.phrs.2020.105367","article-title":"Novel selective hexokinase 2 inhibitor Benitrobenrazide blocks cancer cells growth by targeting glycolysis","volume":"164","author":"Zheng","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12943-024-02024-9","article-title":"New-generation advanced PROTACs as potential therapeutic agents in cancer therapy","volume":"23","author":"Wang","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3892\/ol.2013.1599","article-title":"Differential phosphofructokinase-1 isoenzyme patterns associated with glycolytic efficiency in human breast cancer and paracancer tissues","volume":"6","author":"Wang","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"71471","DOI":"10.18632\/oncotarget.17277","article-title":"Reduced production and uptake of lactate are essential for the ability of WNT5A signaling to inhibit breast cancer cell migration and invasion","volume":"8","author":"Prasad","year":"2017","journal-title":"Oncotarget"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"112282","DOI":"10.1016\/j.yexcr.2020.112282","article-title":"Prognostic and therapeutic relevance of phosphofructokinase platelet-type (PFKP) in breast cancer","volume":"396","author":"Umar","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Yeerken, D., Hong, R., Wang, Y., Gong, Y., Liu, R., Yang, D., Li, J., Fan, J., Chen, J., and Zhang, W. (2020). PFKP is transcriptionally repressed by BRCA1\/ZBRK1 and predicts prognosis in breast cancer. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0233750"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12943-024-02051-6","article-title":"A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression","volume":"23","author":"Liu","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.cell.2012.01.058","article-title":"Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism","volume":"149","author":"Ying","year":"2012","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.molcel.2018.03.018","article-title":"EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation","volume":"70","author":"Lee","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/or.2021.8220","article-title":"Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer","volume":"47","author":"Inaishi","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13058-024-01767-z","article-title":"PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression","volume":"26","author":"Peng","year":"2024","journal-title":"Breast Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12964-020-00679-7","article-title":"Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression","volume":"19","author":"Fan","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41421-022-00406-1","article-title":"PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation","volume":"8","author":"Chen","year":"2022","journal-title":"Cell Discov."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"53562","DOI":"10.1074\/jbc.M406096200","article-title":"6-Phosphofructo-2-kinase (pfkfb3) Gene Promoter Contains Hypoxia-inducible Factor-1 Binding Sites Necessary for Transactivation in Response to Hypoxia","volume":"279","author":"Obach","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1074\/jbc.M113.529990","article-title":"Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-kinase (PFKFB3)","volume":"289","author":"Clem","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"38067","DOI":"10.1038\/srep38067","article-title":"p53 coordinates DNA repair with nucleotide synthesis by suppressing PFKFB3 expression and promoting the pentose phosphate pathway","volume":"6","author":"Franklin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10530","DOI":"10.1074\/jbc.RA119.007784","article-title":"Increased 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase-3 activity in response to EGFR signaling contributes to non\u2013small cell lung cancer cell survival","volume":"294","author":"Lypova","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10549-016-3968-8","article-title":"Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and the growth of HER2+ breast cancer","volume":"160","author":"Clem","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1042\/BJ20130560","article-title":"Adapting glycolysis to cancer cell proliferation: The MAPK pathway focuses on PFKFB3","volume":"452","year":"2013","journal-title":"Biochem. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40170-021-00270-9","article-title":"Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer","volume":"9","author":"Cargill","year":"2021","journal-title":"Cancer Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1158\/0008-5472.CAN-19-3281","article-title":"p38\u03b3 MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis","volume":"80","author":"Wang","year":"2020","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"36020","DOI":"10.1074\/jbc.M113.510289","article-title":"Increased Concentrations of Fructose 2,6-Bisphosphate Contribute to the Warburg Effect in Phosphatase and Tensin Homolog (PTEN)-deficient Cells","volume":"288","author":"Hagen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/s41467-020-15112-3","article-title":"Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming","volume":"11","author":"Liu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_106","first-page":"945","article-title":"PFKFB3 is involved in breast cancer proliferation, migration, invasion and angiogenesis","volume":"52","author":"Peng","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1038\/s41467-019-11640-9","article-title":"Autophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression","volume":"10","author":"Flynn","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s12885-025-13703-1","article-title":"The potential radiosensitization target PFKFB3 is related to response to radiotherapy in SweBCG91RT: A randomized clinical trial with long-term follow-up","volume":"25","author":"Egelberg","year":"2025","journal-title":"BMC Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e400","DOI":"10.1002\/ctm2.400","article-title":"Positive regulation of PFKFB3 by PIM2 promotes glycolysis and paclitaxel resistance in breast cancer","volume":"11","author":"Lu","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1158\/1535-7163.MCT-07-0482","article-title":"Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth","volume":"7","author":"Clem","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Sengupta, S., Sevigny, C.M., Liu, X., Jin, L., and Pohlmann, P.R. (2018). Targeting glycolysis enzyme, PFKFB3, in endocrine therapy resistant breast cancers. Proceedings of the American Association for Cancer Research Annual Meeting, Chicago, IL, USA, 14-18 Apr 2018, AACR. Cancer Research.","DOI":"10.1158\/1538-7445.AM2018-907"},{"key":"ref_112","unstructured":"Sucheta, T., Yaddanapudi, K., Grewal, J., Redman, R., Fu, S., Pohlmann, P., Mahalingam, D., Kurman, M., Tapolsky, G., and Chesney, J. (2016). PFK-158 is a first-in-human inhibitor of PFKFB3 that selectively suppresses glucose metabolism of cancer cells and inhibits the immunosuppressive Th17 cells and MDSCs in advanced cancer patients. Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care, Orlando, FL, USA, 12-15 May 2016, AACR. Cancer Research."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1159\/000495055","article-title":"PFKFB4 Promotes Breast Cancer Metastasis via Induction of Hyaluronan Production in a p38-Dependent Manner","volume":"50","author":"Gao","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12935-019-0882-2","article-title":"High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer","volume":"19","author":"Yao","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"111756","DOI":"10.1016\/j.celrep.2022.111756","article-title":"Hypoxic activation of PFKFB4 in breast tumor microenvironment shapes metabolic and cellular plasticity to accentuate metastatic competence","volume":"41","author":"Dai","year":"2022","journal-title":"Cell Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"8824589","DOI":"10.1155\/2021\/8824589","article-title":"PFKFB4 Overexpression Facilitates Proliferation by Promoting the G1\/S Transition and Is Associated with a Poor Prognosis in Triple-Negative Breast Cancer","volume":"2021","author":"Cai","year":"2021","journal-title":"Dis. Markers"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.bbrc.2016.05.026","article-title":"HIF-1\u03b1 activates hypoxia-induced PFKFB4 expression in human bladder cancer cells","volume":"476","author":"Zhang","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.jcmgh.2023.02.004","article-title":"PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner","volume":"15","author":"Kam","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Kar, S., Maji, N., Sen, K., Roy, S., Maity, A., Dastidar, S.G., Nath, S., Basu, G., and Basu, M. (2023). Reprogramming of glucose metabolism via PFKFB4 is critical in FGF16-driven invasion of breast cancer cells. Biosci. Rep., 43.","DOI":"10.1042\/BSR20230677"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.7150\/thno.28721","article-title":"CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism","volume":"8","author":"Gao","year":"2018","journal-title":"Theranostics"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Wang, S., Bei, Y., Tian, Q., He, J., Wang, R., Wang, Q., Sun, L., Ke, J., Xie, C., and Shen, P. (2022). PFKFB4 facilitates palbociclib resistance in oestrogen receptor-positive breast cancer by enhancing stemness. Cell Prolif., 56.","DOI":"10.1111\/cpr.13337"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"212","DOI":"10.7150\/jca.66773","article-title":"PFKFB4 promotes angiogenesis via IL-6\/STAT5A\/P-STAT5 signaling in breast cancer","volume":"13","author":"Li","year":"2022","journal-title":"J. Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.18632\/oncotarget.4534","article-title":"Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor","volume":"6","author":"Chesney","year":"2015","journal-title":"Oncotarget"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ejca.2022.11.032","article-title":"Rationale for LDH-targeted cancer immunotherapy","volume":"181","author":"Miholjcic","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1126\/science.139.3555.602","article-title":"Lactic and Malic Dehydrogenases in Human Spermatozoa","volume":"139","author":"Goldberg","year":"1963","journal-title":"Science"},{"key":"ref_126","first-page":"6750","article-title":"Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer","volume":"62","author":"Koslowski","year":"2002","journal-title":"Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Pelizzari, G., Basile, D., Zago, S., Lisanti, C., Bartoletti, M., Bortot, L., Vitale, M.G., Fanotto, V., Barban, S., and Cinausero, M. (2019). Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for a Cost-Effective and Dynamic Biomarker. Cancers, 11.","DOI":"10.3390\/cancers11091243"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"10714","DOI":"10.18632\/oncotarget.24246","article-title":"An explorative analysis of the prognostic value of lactate dehydrogenase for survival and the chemotherapeutic response in patients with advanced triple-negative breast cancer","volume":"9","author":"Jia","year":"2018","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.2147\/CMAR.S199260","article-title":"Prognostic significance of serum lactate dehydrogenase in patients with breast cancer: A meta-analysis","volume":"ume 11","author":"Liu","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1158\/1078-0432.CCR-12-1397","article-title":"Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients","volume":"18","author":"Brown","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_131","first-page":"157","article-title":"Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression","volume":"ume 17","author":"Fang","year":"2025","journal-title":"Breast Cancer: Targets Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6069","DOI":"10.1038\/s41598-017-06378-7","article-title":"Tumor LDH-A expression and serum LDH status are two metabolic predictors for triple negative breast cancer brain metastasis","volume":"7","author":"Dong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1186\/s12905-025-04039-w","article-title":"Lactate dehydrogenase a is a crucial biomarker that affects the prognosis, chemotherapy effect, and immune infiltration of breast cancer","volume":"25","author":"Xia","year":"2025","journal-title":"BMC Women\u2019s Health"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.breast.2016.08.014","article-title":"High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer","volume":"30","author":"Huang","year":"2016","journal-title":"Breast"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/cas.13928","article-title":"p53\/Lactate dehydrogenase A axis negatively regulates aerobic glycolysis and tumor progression in breast cancer expressing wild-type p53","volume":"110","author":"Zhou","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6658","DOI":"10.1073\/pnas.94.13.6658","article-title":"c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth","volume":"94","author":"Shim","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s12032-015-0633-8","article-title":"The c-Myc\u2013LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer","volume":"32","author":"He","year":"2015","journal-title":"Med Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Privat, M., Radosevic-Robin, N., Aubel, C., Cayre, A., Penault-Llorca, F., Marceau, G., Sapin, V., Bignon, Y.-J., and Morvan, D. (2014). BRCA1 Induces Major Energetic Metabolism Reprogramming in Breast Cancer Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102438"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1038\/onc.2009.229","article-title":"Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth","volume":"28","author":"Zhao","year":"2009","journal-title":"Oncogene"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1038\/onc.2017.6","article-title":"Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis","volume":"36","author":"Jin","year":"2017","journal-title":"Oncogene"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1186\/s12967-024-05517-9","article-title":"Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer","volume":"22","author":"Papulino","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5158","DOI":"10.1158\/1078-0432.CCR-12-3300","article-title":"Relationships between LDH-A, Lactate, and Metastases in 4T1 Breast Tumors","volume":"19","author":"Rizwan","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0021-9258(18)98146-9","article-title":"Lactic dehydrogenase. V. Inhibition by oxamate and by oxalate","volume":"234","author":"Novoa","year":"1959","journal-title":"J. Biol. Chem."},{"key":"ref_144","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_145","doi-asserted-by":"crossref","first-page":"120088","DOI":"10.1016\/j.bbamcr.2025.120088","article-title":"Anti-tumor response by targeting glucose metabolism and depletion of membrane cholesterol in breast cancer and melanoma cells","volume":"1873","author":"Yaduvanshi","year":"2025","journal-title":"Biochim. et Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/j.biopha.2017.09.090","article-title":"Oxamate potentiates taxol chemotherapeutic efficacy in experimentally-induced solid ehrlich carcinoma (SEC) in mice","volume":"95","author":"Sokar","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"R84","DOI":"10.1186\/bcr2154","article-title":"Targeting aspartate aminotransferase in breast cancer","volume":"10","author":"Thornburg","year":"2008","journal-title":"Breast Cancer Res."},{"key":"ref_148","first-page":"6605","article-title":"Targeting the monocarboxylate transporter MCT2 and lactate dehydrogenase A LDHA in cancer cells with FX-11 and AR-C155858 inhibitors","volume":"27","author":"Alobaidi","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Hashimoto, T., Ushikubo, G., Arao, N., Hatabi, K., Tsubota, K., and Hosoi, Y. (2025). Oxamate, an LDHA Inhibitor, Inhibits Stemness, Including EMT and High DNA Repair Ability, Induces Senescence, and Exhibits Radiosensitizing Effects in Glioblastoma Cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125710"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1111\/cas.15468","article-title":"Development of a novel lactate dehydrogenase A inhibitor with potent antitumor activity and immune activation","volume":"113","author":"Du","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Qiao, T., Xiong, Y., Feng, Y., Guo, W., Zhou, Y., Zhao, J., Jiang, T., Shi, C., and Han, Y. (2021). Inhibition of LDH-A by Oxamate Enhances the Efficacy of Anti-PD-1 Treatment in an NSCLC Humanized Mouse Model. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.632364"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Verma, S., Budhu, S., Serganova, I., Dong, L., Mangarin, L.M., Khan, J.F., Bah, M.A., Assouvie, A., Marouf, Y., and Schulze, I. (2024). Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models. J. Clin. Investig., 134.","DOI":"10.1172\/JCI177606"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1476-4598-9-33","article-title":"Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol","volume":"9","author":"Zhou","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1158\/1078-0432.CCR-13-0623","article-title":"Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer","volume":"19","author":"Dennison","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_155","first-page":"513","article-title":"Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression","volume":"21","author":"Luo","year":"2024","journal-title":"Cancer Biol. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"662","DOI":"10.18632\/oncotarget.2689","article-title":"Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers","volume":"6","author":"Arora","year":"2015","journal-title":"Oncotarget"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/1878-0261.13024","article-title":"Targeting of lactate dehydrogenase C dysregulates the cell cycle and sensitizes breast cancer cells to DNA damage response targeted therapy","volume":"16","author":"Naik","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12964-025-02139-6","article-title":"Immunomodulatory effects of tumor Lactate Dehydrogenase C (LDHC) in breast cancer","volume":"23","author":"Naik","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Qasem, H., Naik, A., Gomez, T., Ponraj, J., Jafar, U., Sikhondze, M., Thomas, R., Mahmoud, K.A., and Decock, J. (2025). Anti-tumor effects of a novel cell penetrating peptide-based therapeutic approach to target Lactate Dehydrogenase C (LDHC) in triple negative breast cancer. bioRxiv.","DOI":"10.1101\/2025.03.11.641612"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.jbc.2022.102838","article-title":"Regulation and function of the mammalian tricarboxylic acid cycle","volume":"299","author":"Arnold","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1038\/s41388-020-01639-8","article-title":"The functional roles of TCA cycle metabolites in cancer","volume":"40","author":"Eniafe","year":"2021","journal-title":"Oncogene"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.semcdb.2019.05.031","article-title":"The multifaceted contribution of \u03b1-ketoglutarate to tumor progression: An opportunity to exploit?","volume":"98","author":"Abla","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_163","first-page":"21","article-title":"Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use","volume":"65","year":"2016","journal-title":"Arch. Immunol. et Ther. Exp."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"19611","DOI":"10.1073\/pnas.1117773108","article-title":"Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of \u03b1-ketoglutarate to citrate to support cell growth and viability","volume":"108","author":"Wise","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cmet.2013.02.002","article-title":"In Vivo HIF-Mediated Reductive Carboxylation Is Regulated by Citrate Levels and Sensitizes VHL-Deficient Cells to Glutamine Deprivation","volume":"17","author":"Gameiro","year":"2013","journal-title":"Cell Metab."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.celrep.2014.04.037","article-title":"Oxidation of Alpha-Ketoglutarate Is Required for Reductive Carboxylation in Cancer Cells with Mitochondrial Defects","volume":"7","author":"Mullen","year":"2014","journal-title":"Cell Rep."},{"key":"ref_167","first-page":"27","article-title":"Effect of Alpha-ketoglutarate on the proliferation behavior of breast cancer cells in vitro","volume":"37","author":"TALKHABI","year":"2024","journal-title":"Appl. Biol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1158\/0008-5472.CAN-17-2906","article-title":"Transketolase Regulates the Metabolic Switch to Control Breast Cancer Cell Metastasis via the \u03b1-Ketoglutarate Signaling Pathway","volume":"78","author":"Tseng","year":"2018","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/s41419-018-0802-8","article-title":"\u03b1-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis","volume":"9","author":"Atlante","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_170","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_171","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ccr.2013.03.005","article-title":"R-2-Hydroxyglutarate as the Key Effector of IDH Mutations Promoting Oncogenesis","volume":"23","author":"Ye","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of \u03b1-Ketoglutarate-Dependent Dioxygenases","volume":"19","author":"Xu","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1634\/theoncologist.2013-0417","article-title":"Isocitrate Dehydrogenase 1 (IDH1) Mutation in Breast Adenocarcinoma Is Associated with Elevated Levels of Serum and Urine 2-Hydroxyglutarate","volume":"19","author":"Fathi","year":"2014","journal-title":"Oncologist"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"7118","DOI":"10.1158\/0008-5472.CAN-16-0298","article-title":"IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity","volume":"76","author":"Chiang","year":"2016","journal-title":"Cancer Res."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"\u0160pa\u010dkov\u00e1, J., Gotvaldov\u00e1, K., Dvo\u0159\u00e1k, A., Urban\u010dokov\u00e1, A., Posp\u00ed\u0161ilov\u00e1, K., V\u011btvi\u010dka, D., Leguina-Ruzzi, A., Tesa\u0159ov\u00e1, P., V\u00edtek, L., and Je\u017eek, P. (2021). Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma. Cancers, 13.","DOI":"10.20944\/preprints202103.0007.v1"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10549-019-05459-7","article-title":"The prognostic significance of wild-type isocitrate dehydrogenase 2 (IDH2) in breast cancer","volume":"179","author":"Aljohani","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s12282-021-01228-x","article-title":"Isoforms of IDH in breast carcinoma: IDH2 as a potent prognostic factor associated with proliferation in estrogen-receptor positive cases","volume":"28","author":"Minemura","year":"2021","journal-title":"Breast Cancer"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1038\/s41467-024-47536-6","article-title":"Wild-type IDH2 is a therapeutic target for triple-negative breast cancer","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.1234769","article-title":"Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation","volume":"340","author":"Wang","year":"2013","journal-title":"Science"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1172\/JCI71180","article-title":"MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis","volume":"124","author":"Terunuma","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.trecan.2017.12.005","article-title":"Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates","volume":"4","author":"Ye","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-025-01186-y","article-title":"TCA cycle-derived oncometabolites in cancer and the immune microenvironment","volume":"32","author":"Sarkar","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature13909","article-title":"Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS","volume":"515","author":"Chouchani","year":"2014","journal-title":"Nature"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1016\/j.celrep.2018.04.104","article-title":"Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity","volume":"23","author":"Zhang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1086\/324413","article-title":"The R22X Mutation of the SDHD Gene in Hereditary Paraganglioma Abolishes the Enzymatic Activity of Complex II in the Mitochondrial Respiratory Chain and Activates the Hypoxia Pathway","volume":"69","author":"Favier","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-\u03b1 prolyl hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.molcel.2019.10.023","article-title":"Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor","volume":"77","author":"Wu","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"G\u00f3mez, V., Eykyn, T.R., Mustapha, R., Flores-Borja, F., Male, V., Barber, P.R., Patsialou, A., Green, R., Panagaki, F., and Li, C.W. (2020). Breast cancer\u2013associated macrophages promote tumorigenesis by suppressing succinate dehydrogenase in tumor cells. Sci. Signal., 13.","DOI":"10.1126\/scisignal.aax4585"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"32054","DOI":"10.18632\/oncotarget.8410","article-title":"A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ajhg.2008.07.011","article-title":"Germline Mutations and Variants in the Succinate Dehydrogenase Genes in Cowden and Cowden-like Syndromes","volume":"83","author":"Ni","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"5221","DOI":"10.62347\/XAKQ8090","article-title":"Exploring the critical role of SDHA in breast cancer proliferation: Implications for novel therapeutic strategies","volume":"17","author":"Khan","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/2193-1801-2-299","article-title":"Succinate dehydrogenase expression in breast cancer","volume":"2","author":"Kim","year":"2013","journal-title":"SpringerPlus"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12935-025-03746-6","article-title":"Unveiling the hidden role of SDHA in breast cancer proliferation: A novel therapeutic avenue","volume":"25","author":"Yong","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40170-019-0197-8","article-title":"Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC","volume":"7","author":"Dyrstad","year":"2019","journal-title":"Cancer Metab."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1038\/s41416-023-02412-w","article-title":"Fumarate hydratase (FH) and cancer: A paradigm of oncometabolism","volume":"129","author":"Frezza","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ymben.2017.11.011","article-title":"Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells","volume":"45","author":"Sciacovelli","year":"2018","journal-title":"Metab. Eng."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.celrep.2013.04.006","article-title":"A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia","volume":"3","author":"Adam","year":"2013","journal-title":"Cell Rep."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.cmet.2023.04.017","article-title":"Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8+ T cells in the tumor microenvironment","volume":"35","author":"Cheng","year":"2023","journal-title":"Cell Metab."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2006.03.005","article-title":"S-(2-Succinyl)cysteine: A novel chemical modification of tissue proteins by a Krebs cycle intermediate","volume":"450","author":"Alderson","year":"2006","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.molcel.2022.01.029","article-title":"Fumarate inhibits PTEN to promote tumorigenesis and therapeutic resistance of type2 papillary renal cell carcinoma","volume":"82","author":"Ge","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40170-025-00397-z","article-title":"Oncogenic role of fumarate hydratase in breast cancer: Metabolic reprogramming and mechanistic insights","volume":"13","author":"Yuan","year":"2025","journal-title":"Cancer Metab."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/sj.ejhg.5201326","article-title":"No germline FH mutations in familial breast cancer patients","volume":"13","author":"Kiuru","year":"2004","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.semcdb.2019.05.002","article-title":"Fumarate hydratase in cancer: A multifaceted tumour suppressor","volume":"98","author":"Schmidt","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1021\/ja5101257","article-title":"Identification of Fumarate Hydratase Inhibitors with Nutrient-Dependent Cytotoxicity","volume":"137","author":"Takeuchi","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"ref_205","first-page":"257","article-title":"Malate dehydrogenases\u2014structure and function","volume":"21","year":"2002","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Lou, Y., Lou, Y., Cheng, Y., Xu, B., Chen, H., and Dai, Y. (2025). Panoramic view of MDH1: Driving cancer progression and shaping the tumor immune microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1631449"},{"key":"ref_207","first-page":"3557","article-title":"Multi-Omics Insights into the Impact of MDH2 on Breast Cancer Progression: A Promising Druggable Target","volume":"33","author":"Pan","year":"2025","journal-title":"Oncol. Res. Featur. Preclin. Clin. Cancer Ther."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Cannon-Albright, L.A., Stevens, J., Teerlink, C.C., Facelli, J.C., Allen-Brady, K., and Welm, A.L. (2023). A Rare Variant in MDH2 (rs111879470) Is Associated with Predisposition to Recurrent Breast Cancer in an Extended High-Risk Pedigree. Cancers, 15.","DOI":"10.3390\/cancers15245851"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tranon.2017.01.009","article-title":"MDH2 Stimulated by Estrogen-GPR30 Pathway Down-Regulated PTEN Expression Promoting the Proliferation and Invasion of Cells in Endometrial Cancer","volume":"10","author":"Zhuang","year":"2017","journal-title":"Transl. Oncol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e0162568","DOI":"10.1371\/journal.pone.0162568","article-title":"A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Inducible Factor-1 by Regulating Mitochondrial Respiration","volume":"11","author":"Ban","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"9522","DOI":"10.1021\/jm501241g","article-title":"Synthesis and Structure\u2013Activity Relationship Study of Chemical Probes as Hypoxia Induced Factor-1\u03b1\/Malate Dehydrogenase 2 Inhibitors","volume":"57","author":"Naik","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.abb.2016.12.012","article-title":"The regulation of the pentose phosphate pathway: Remember Krebs","volume":"614","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.tibs.2014.06.005","article-title":"The pentose phosphate pathway and cancer","volume":"39","author":"Patra","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S1369-5266(03)00039-6","article-title":"The oxidative pentose phosphate pathway: Structure and organisation","volume":"6","author":"Kruger","year":"2003","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/brv.12140","article-title":"The return of metabolism: Biochemistry and physiology of the pentose phosphate pathway","volume":"90","author":"Stincone","year":"2015","journal-title":"Biol. Rev."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(94)01368-B","article-title":"Persistent oxidative stress in cancer","volume":"358","author":"Toyokuni","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_217","first-page":"794","article-title":"Production of large amounts of hydrogen peroxide by human tumor cells","volume":"51","author":"Szatrowski","year":"1991","journal-title":"Cancer Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4331\/wjbc.v6.i3.148","article-title":"Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication","volume":"6","author":"Lee","year":"2015","journal-title":"World J. Biol. Chem."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.freeradbiomed.2012.05.006","article-title":"The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate","volume":"53","author":"Riganti","year":"2012","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00018-023-04810-y","article-title":"G6PD activation in TNBC cells induces macrophage recruitment and M2 polarization to promote tumor progression","volume":"80","author":"Li","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Zeng, T., Li, B., Shu, X., Pang, J., Wang, H., Cai, X., Liao, Y., Xiao, X., Chong, Y., and Gong, J. (2023). Pan-cancer analysis reveals that G6PD is a prognostic biomarker and therapeutic target for a variety of cancers. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1183474"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/febs.16614","article-title":"Targeting glucose-6-phosphate dehydrogenase by 6-AN induces ROS-mediated autophagic cell death in breast cancer","volume":"290","author":"Li","year":"2022","journal-title":"FEBS J."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.bbabio.2010.11.015","article-title":"Carbon metabolism and the sign of control coefficients in metabolic adaptations underlying K-ras transformation","volume":"1807","author":"Benito","year":"2011","journal-title":"Biochim. et Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s13046-017-0637-7","article-title":"ID1 promotes hepatocellular carcinoma proliferation and confers chemoresistance to oxaliplatin by activating pentose phosphate pathway","volume":"36","author":"Yin","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1136\/gutjnl-2013-305302","article-title":"PTEN antagonises Tcl1\/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis","volume":"63","author":"Hong","year":"2013","journal-title":"Gut"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.febslet.2004.06.004","article-title":"Induction of the glucose-6-phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells","volume":"569","author":"Gao","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"L287","DOI":"10.1152\/ajplung.00229.2014","article-title":"Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: Implication in pulmonary hypertension","volume":"308","author":"Chettimada","year":"2015","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1111\/jcmm.14241","article-title":"Nrf2 promotes breast cancer cell migration via up-regulation of G6PD\/HIF-1\u03b1\/Notch1 axis","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.7150\/ijbs.65555","article-title":"High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level","volume":"18","author":"Luo","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"106693","DOI":"10.18632\/oncotarget.21601","article-title":"Glucose-6-phosphate dehydrogenase and transketolase modulate breast cancer cell metabolic reprogramming and correlate with poor patient outcome","volume":"8","author":"Benito","year":"2017","journal-title":"Oncotarget"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13046-019-1164-5","article-title":"Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation","volume":"38","author":"Mele","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41419-018-0635-5","article-title":"A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo","volume":"9","author":"Mele","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s12094-018-1833-4","article-title":"Inhibiting 6-phosphogluconate dehydrogenase selectively targets breast cancer through AMPK activation","volume":"20","author":"Yang","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Polat, I.H., Tarrado-Castellarnau, M., Bharat, R., Perarnau, J., Benito, A., Cort\u00e9s, R., Sabatier, P., and Cascante, M. (2021). Oxidative Pentose Phosphate Pathway Enzyme 6-Phosphogluconate Dehydrogenase Plays a Key Role in Breast Cancer Metabolism. Biology, 10.","DOI":"10.3390\/biology10020085"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/ncb3255","article-title":"6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1\u2013AMPK signalling","volume":"17","author":"Lin","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"9369358","DOI":"10.1155\/2018\/9369358","article-title":"Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer","volume":"2018","author":"Choi","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1136\/bmj.2.5711.698","article-title":"Enzyme Activity, Acidic Nuclear Proteins, and Prognosis in Human Breast Cancer","volume":"2","author":"Smith","year":"1970","journal-title":"BMJ"},{"key":"ref_238","first-page":"99","article-title":"The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a marker of tumour cellularity and prognostic indicator in primary breast cancer","volume":"7","author":"Brocklehurst","year":"1986","journal-title":"Tumor Biol."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Xu, J., Ren, G., and Cheng, Q. (2023). Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells. Technol. Cancer Res. Treat., 22.","DOI":"10.1177\/15330338231190737"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"R146","DOI":"10.1152\/ajpregu.1984.247.1.R146","article-title":"Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor","volume":"247","author":"Ookhtens","year":"1984","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Schulze","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1158\/0008-5472.CAN-11-4112","article-title":"ATP-Citrate Lyase: A Key Player in Cancer Metabolism","volume":"72","author":"Zaidi","year":"2012","journal-title":"Cancer Res."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s12276-020-00504-8","article-title":"Glutamine reliance in cell metabolism","volume":"52","author":"Yoo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1002\/jcp.25332","article-title":"Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered","volume":"231","author":"Kinlaw","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.mito.2018.02.009","article-title":"Mitochondrial \u03b2-oxidation of saturated fatty acids in humans","volume":"46","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Liang, K. (2023). Mitochondrial CPT1A: Insights into structure, function, and basis for drug development. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1160440"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"zcab035","DOI":"10.1093\/narcan\/zcab035","article-title":"CPT1A and fatty acid \u03b2-oxidation are essential for tumor cell growth and survival in hormone receptor-positive breast cancer","volume":"3","author":"Jariwala","year":"2021","journal-title":"NAR Cancer"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1186\/s12885-021-08134-7","article-title":"Carnitine palmitoyl transferase 1A is a novel diagnostic and predictive biomarker for breast cancer","volume":"21","author":"Tan","year":"2021","journal-title":"BMC Cancer"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.7150\/thno.21451","article-title":"Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy","volume":"8","author":"Tan","year":"2018","journal-title":"Theranostics"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/j.celrep.2016.02.004","article-title":"Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer","volume":"14","author":"Park","year":"2016","journal-title":"Cell Rep."},{"key":"ref_251","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_252","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13058-015-0528-9","article-title":"Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth","volume":"17","author":"Ren","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_253","first-page":"69","article-title":"Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis\/prognosis marker","volume":"1","author":"Liu","year":"2010","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/09553002.2024.2446585","article-title":"FASN inhibition shows the potential for enhancing radiotherapy outcomes by targeting glycolysis, AKT, and ERK pathways in breast cancer","volume":"101","author":"Chen","year":"2025","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/(SICI)1097-0142(19960201)77:3<474::AID-CNCR8>3.0.CO;2-K","article-title":"Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients","volume":"77","author":"Alo","year":"1996","journal-title":"Cancer"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"32576","DOI":"10.18632\/oncotarget.15936","article-title":"NADPH accumulation is responsible for apoptosis in breast cancer cells induced by fatty acid synthase inhibition","volume":"8","author":"Cui","year":"2017","journal-title":"Oncotarget"},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Liu, B., Peng, Q., Wang, Y.-W., Qiu, J., Zhu, J., and Ma, R. (2023). Prognostic and clinicopathological significance of fatty acid synthase in breast cancer: A systematic review and meta-analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1153076"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ol.2020.12288","article-title":"Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism","volume":"21","author":"Xu","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40170-025-00404-3","article-title":"Fatty acid synthase-derived lipid stores support breast cancer metastasis","volume":"13","author":"Andolino","year":"2025","journal-title":"Cancer Metab."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s43018-021-00183-y","article-title":"Fatty acid synthesis is required for breast cancer brain metastasis","volume":"2","author":"Ferraro","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/1476-4598-13-138","article-title":"Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells","volume":"13","author":"Li","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s10549-021-06231-6","article-title":"FASN inhibition as a potential treatment for endocrine-resistant breast cancer","volume":"187","author":"Gruslova","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41523-024-00656-0","article-title":"Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion","volume":"10","author":"Serhan","year":"2024","journal-title":"NPJ Breast Cancer"},{"key":"ref_264","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_265","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41420-024-02184-z","article-title":"Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity","volume":"10","author":"Pedarra","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"e010924","DOI":"10.1136\/jitc-2024-010924","article-title":"Targeting B7-H3 inhibition-induced activation of fatty acid synthesis boosts anti-B7-H3 immunotherapy in triple-negative breast cancer","volume":"13","author":"Jiang","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Scalise, M., Pochini, L., Galluccio, M., Console, L., and Indiveri, C. (2017). Glutamine Transport and Mitochondrial Metabolism in Cancer Cell Growth. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00306"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s12276-023-00971-9","article-title":"Targeting glutamine metabolism as a therapeutic strategy for cancer","volume":"55","author":"Jin","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"e2000169","DOI":"10.1002\/bies.202000169","article-title":"A second Warburg-like effect in cancer metabolism: The metabolic shift of glutamine-derived nitrogen","volume":"42","author":"Kodama","year":"2020","journal-title":"BioEssays"},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1158\/1078-0432.CCR-14-1200","article-title":"Targeting Glutamine Metabolism in Breast Cancer with Aminooxyacetate","volume":"21","author":"Korangath","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_271","first-page":"3201","article-title":"ASCT2\/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer","volume":"35","author":"Wang","year":"2015","journal-title":"Oncogene"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1530\/ERC-12-0398","article-title":"Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer","volume":"20","author":"Kim","year":"2013","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1038\/s41598-025-87292-1","article-title":"SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer","volume":"15","author":"Alfarsi","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"777","DOI":"10.21037\/atm-22-2620","article-title":"Bioinformatic analysis of the role of solute carrier-glutamine transporters in breast cancer","volume":"10","author":"Zhao","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10549-021-06298-1","article-title":"SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer","volume":"189","author":"Alfarsi","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"18782","DOI":"10.1073\/pnas.0810199105","article-title":"Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction","volume":"105","author":"Wise","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cmet.2019.11.020","article-title":"A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells","volume":"31","author":"Yoo","year":"2020","journal-title":"Cell Metab."},{"key":"ref_278","first-page":"94","article-title":"Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer","volume":"122","author":"Craze","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00280-010-1316-y","article-title":"Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake","volume":"67","author":"Todorova","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Aquilano, K., Baldelli, S., and Ciriolo, M.R. (2014). Glutathione: New roles in redox signaling for an old antioxidant. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00196"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s12282-023-01502-0","article-title":"Glutaminase (GLS1) gene expression in primary breast cancer","volume":"30","author":"Vidula","year":"2023","journal-title":"Breast Cancer"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/1476-4598-13-239","article-title":"MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer","volume":"13","author":"Cook","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"7455","DOI":"10.1073\/pnas.1001006107","article-title":"Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function","volume":"107","author":"Hu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_284","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_285","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.gendis.2022.02.009","article-title":"Targeting glutamine metabolism enhances responses to platinum-based chemotherapy in triple-negative breast cancers (TNBC)","volume":"9","author":"Hong","year":"2022","journal-title":"Genes Dis."},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Masisi, B.K., El Ansari, R., Alfarsi, L., Craze, M.L., Jewa, N., Oldfield, A., Cheung, H., Toss, M., Rakha, E.A., and Green, A.R. (2021). The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13163963"},{"key":"ref_287","doi-asserted-by":"crossref","unstructured":"Kung, H.-N., Marks, J.R., and Chi, J.-T. (2011). Glutamine Synthetase Is a Genetic Determinant of Cell Type\u2013Specific Glutamine Independence in Breast Epithelia. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002229"},{"key":"ref_288","doi-asserted-by":"crossref","unstructured":"Demas, D.M., Demo, S., Fallah, Y., Clarke, R., Nephew, K.P., Althouse, S., Sandusky, G., He, W., and Shajahan-Haq, A.N. (2019). Glutamine Metabolism Drives Growth in Advanced Hormone Receptor Positive Breast Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00686"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccr.2013.08.020","article-title":"Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target","volume":"24","author":"Timmerman","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"115464","DOI":"10.1016\/j.bcp.2023.115464","article-title":"Glutamine metabolism in breast cancer and possible therapeutic targets","volume":"210","author":"Li","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"e70036","DOI":"10.1111\/cpr.70036","article-title":"Glutaminase-1 Mediated Glutaminolysis to Glutathione Synthesis Maintains Redox Homeostasis and Modulates Ferroptosis Sensitivity in Cancer Cells","volume":"58","author":"Bai","year":"2025","journal-title":"Cell Prolif."},{"key":"ref_292","first-page":"587","article-title":"Down-regulation of GLS1 inhibits proliferation, clonogenicity and migration of agressive MDA-MB-231 Breast Cancer Cells by increasing p21 and decreasing Integrin- \u03b21","volume":"44","author":"Akar","year":"2022","journal-title":"Turk. J. Trauma Emerg. Surg."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/jcb.24684","article-title":"ErbB2 Activation Upregulates Glutaminase 1 Expression Which Promotes Breast Cancer Cell Proliferation","volume":"115","author":"Qie","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Edwards, D.N., Ngwa, V.M., Raybuck, A.L., Wang, S., Hwang, Y., Kim, L.C., Cho, S.H., Paik, Y., Wang, Q., and Zhang, S. (2021). Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J. Clin. Investig., 131.","DOI":"10.1172\/JCI140100"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"e0185092","DOI":"10.1371\/journal.pone.0185092","article-title":"Glutaminase is essential for the growth of triple-negative breast cancer cells with a deregulated glutamine metabolism pathway and its suppression synergizes with mTOR inhibition","volume":"12","author":"Lampa","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.3892\/mmr.2015.3261","article-title":"Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol","volume":"11","author":"Fu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"112772","DOI":"10.1016\/j.isci.2025.112772","article-title":"Glutamate receptor\u2013T cell receptor signaling potentiates full CD8+ T cell activation and effector function in tumor immunity","volume":"28","author":"Hodo","year":"2025","journal-title":"iScience"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.celrep.2019.08.076","article-title":"Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer","volume":"29","author":"Lukey","year":"2019","journal-title":"Cell Rep."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/s41388-019-1007-z","article-title":"GLS2 is protumorigenic in breast cancers","volume":"39","author":"Dias","year":"2019","journal-title":"Oncogene"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"106490","DOI":"10.1016\/j.phrs.2022.106490","article-title":"Therapeutic targeting of glutamate dehydrogenase 1 that links metabolic reprogramming and Snail-mediated epithelial\u2013mesenchymal transition in drug-resistant lung cancer","volume":"185","author":"Wang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10549-018-5060-z","article-title":"Glutamate dehydrogenase (GLUD1) expression in breast cancer","volume":"174","author":"Craze","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_302","unstructured":"Young, T.A., Bahnassy, S., Abalum, T.C., Pope, E.A., Rivera, A.T., Fernandez, A.I., Olukoya, A.O., Mobin, D., Ranjit, S., and Libbey, N.E. (2024). Glutamate Transport Proteins and Metabolic Enzymes are Poor Prognostic Factors in Invasive Lobular Carcinoma. bioRxiv."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ccell.2014.12.006","article-title":"Glutamate Dehydrogenase 1 Signals through Antioxidant Glutathione Peroxidase 1 to Regulate Redox Homeostasis and Tumor Growth","volume":"27","author":"Jin","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1126\/science.aam9305","article-title":"Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass","volume":"358","author":"Spinelli","year":"2017","journal-title":"Science"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1083\/jcb.201604085","article-title":"The importance of serine metabolism in cancer","volume":"214","author":"Mattaini","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.tibs.2014.02.004","article-title":"Serine and glycine metabolism in cancer","volume":"39","author":"Amelio","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_307","doi-asserted-by":"crossref","unstructured":"Zhu, S., Liu, Y., Chen, H., Zhu, X., Liu, X., Xu, K., Sang, Y., Shang, L., Chong, W., and Li, L. (2025). Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer. Clin. Med. Insights Oncol., 19.","DOI":"10.1177\/11795549251331755"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"444","DOI":"10.21037\/tcr-21-2485","article-title":"Serine hydroxymethyltransferase 2 predicts unfavorable outcomes in multiple cancer: A systematic review and meta-analysis","volume":"11","author":"Du","year":"2022","journal-title":"Transl. Cancer Res."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13058-017-0905-7","article-title":"Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors","volume":"19","author":"Bernhardt","year":"2017","journal-title":"Breast Cancer Res."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.3892\/or.2016.5112","article-title":"Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker","volume":"36","author":"Zhang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1158\/1541-7786.MCR-19-0606","article-title":"Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism","volume":"18","author":"Li","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_312","first-page":"3405","article-title":"SHMT2 promotes tumor growth through VEGF and MAPK signaling pathway in breast cancer","volume":"12","author":"Xie","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.1128\/MCB.22.16.5793-5800.2002","article-title":"A Functional Screen for Myc-Responsive Genes Reveals Serine Hydroxymethyltransferase, a Major Source of the One-Carbon Unit for Cell Metabolism","volume":"22","author":"Nikiforov","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1158\/0008-5472.CAN-15-2383","article-title":"HER2 Signaling Drives DNA Anabolism and Proliferation through SRC-3 Phosphorylation and E2F1-Regulated Genes","volume":"76","author":"Nikolai","year":"2016","journal-title":"Cancer Res."},{"key":"ref_315","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, K., Hu, Y., and Luo, N. (2020). ERR\u03b1 activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption. Biosci. Rep., 40.","DOI":"10.1042\/BSR20192465"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1158\/1535-7163.MCT-20-0480","article-title":"Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine\/Glycine Synthesis\u2013Addicted Breast Tumor Growth","volume":"20","author":"Geeraerts","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_317","first-page":"377","article-title":"SHMT inhibition is effective and synergizes with methotrexate in T-cell acute lymphoblastic leukemia","volume":"35","author":"Lancho","year":"2020","journal-title":"Leukemia"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41698-025-00926-5","article-title":"SHMT inhibitor synergizes with 5-Fu to suppress gastric cancer via cell cycle arrest and chemoresistance alleviation","volume":"9","author":"Deng","year":"2025","journal-title":"NPJ Precis. Oncol."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1158\/1535-7163.MCT-23-0550","article-title":"Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer","volume":"23","author":"Dekhne","year":"2024","journal-title":"Mol. Cancer Ther."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/s12276-024-01268-1","article-title":"PHGDH: A novel therapeutic target in cancer","volume":"56","author":"Lee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_321","doi-asserted-by":"crossref","unstructured":"Kim, S.K., Jung, W.H., and Koo, J.S. (2014). Differential Expression of Enzymes Associated with Serine\/Glycine Metabolism in Different Breast Cancer Subtypes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101004"},{"key":"ref_322","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_323","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41586-022-04758-2","article-title":"PHGDH heterogeneity potentiates cancer cell dissemination and metastasis","volume":"605","author":"Rossi","year":"2022","journal-title":"Nature"},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1007\/s13277-013-1588-z","article-title":"Expression levels of serine\/glycine metabolism-related proteins in triple negative breast cancer tissues","volume":"35","author":"Noh","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/ijc.33423","article-title":"Inhibiting phosphoglycerate dehydrogenase counteracts chemotherapeutic efficacy against MYCN-amplified neuroblastoma","volume":"148","author":"Arlt","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"109706","DOI":"10.1016\/j.celrep.2021.109706","article-title":"ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restriction","volume":"36","author":"Li","year":"2021","journal-title":"Cell Rep."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1074\/jbc.M114.616359","article-title":"p53 Protein-mediated Regulation of Phosphoglycerate Dehydrogenase (PHGDH) Is Crucial for the Apoptotic Response upon Serine Starvation","volume":"290","author":"Ou","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"100002","DOI":"10.1016\/j.labinv.2022.100002","article-title":"The Role of ESRP1 in the Regulation of PHGDH in Estrogen Receptor\u2013Positive Breast Cancer","volume":"103","author":"Gu","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s12282-018-0858-4","article-title":"LncRNA PlncRNA-1 overexpression inhibits the growth of breast cancer by upregulating TGF-\u03b21 and downregulating PHGDH","volume":"25","author":"Li","year":"2018","journal-title":"Breast Cancer"},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/ng.890","article-title":"Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis","volume":"43","author":"Locasale","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.18632\/oncotarget.1540","article-title":"Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth","volume":"4","author":"Chen","year":"2013","journal-title":"Oncotarget"},{"key":"ref_332","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_333","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_334","doi-asserted-by":"crossref","first-page":"13139","DOI":"10.18632\/oncotarget.11487","article-title":"Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for fragment-based drug discovery in PHGDH-amplified breast cancer","volume":"9","author":"Unterlass","year":"2016","journal-title":"Oncotarget"},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00280-016-3117-4","article-title":"Repression of phosphoglycerate dehydrogenase sensitizes triple-negative breast cancer to doxorubicin","volume":"78","author":"Zhang","year":"2016","journal-title":"Cancer Chemother. Pharmacol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/2\/129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:23:18Z","timestamp":1771996998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/2\/129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,23]]},"references-count":335,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["curroncol33020129"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33020129","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,23]]}}}