Glucose metabolic dysregulation and oxidative stress in cholangiocarcinoma: molecular mechanisms, oncogenic drivers, and novel therapeutic targets

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy marked by profound glucose metabolic dysregulation and oxidative stress. Central to this reprogramming is the upregulation of glucose transporters such as GLUT1, driving enhanced glycolytic flux, activation of the pentose phosphate pathway (PPP), increased lactate production, and alterations in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). These metabolic shifts support tumor proliferation, redox balance, and stemness, and are closely linked to recurrent oncogenic mutations, including KRAS, TP53, IDH1/2, ARID1A, FGFR2, and HER2. These mutations converge on key signaling networks that promote metabolic plasticity and therapeutic resistance. Recent evidence suggests that targeting metabolic vulnerabilities offers promising avenues for intervention. Inhibitors of glycolytic enzymes (HKII, PKM2), PPP regulators (G6PD, TKT), TCA cycle components [IDH, glutaminase (GLS)], lactate metabolism (LDHA), and OXPHOS machinery (Complex I) have demonstrated potential in preclinical models. Additionally, repurposing antidiabetic drugs such as metformin and SGLT2 inhibitors may offer novel metabolic therapies. Regulatory non-coding RNAs, including microRNAs and long non-coding RNAs, further modulate key enzymes and transporters, highlighting their emerging roles as both biomarkers and therapeutic targets. However, challenges such as tumor heterogeneity, metabolic redundancy, off-target toxicity, and resistance mechanisms continue to hinder clinical translation. Integrated therapeutic approaches combining metabolic inhibitors with chemotherapy, immunotherapy, or targeted agents are likely necessary to overcome these barriers. This review synthesizes the current understanding of glucose metabolism and redox dysregulation in CCA, emphasizing the molecular drivers, therapeutic opportunities, and translational challenges, with the goal of guiding future research toward more effective and personalized treatment strategies.

Keywords

Glucose metabolism dysregulation in CCA / cholangiocarcinoma / oxidative stress / oncogenic drivers / therapeutic targets

References

[1] Banales JM,Lamarca A.Cholangiocarcinoma 2020: the next horizon in mechanisms and management.Nat Rev Gastroenterol Hepatol2020;17:557-88 PMCID:PMC7447603

[2] Brindley PJ,Ilyas SI.Cholangiocarcinoma.Nat Rev Dis Primers2021;7:65 PMCID:PMC9246479

[3] Vithayathil M.Current epidemiology of cholangiocarcinoma in Western countries.J Hepatol2022;77:1690-8

[4] Sripa B.Cholangiocarcinoma: lessons from Thailand.Curr Opin Gastroenterol2008;24:349-56 PMCID:PMC4130346

[5] Treeprasertsuk S,Soonthornworasiri N.A significant cancer burden and high mortality of intrahepatic cholangiocarcinoma in Thailand: a nationwide database study.BMC Gastroenterol2017;17:3 PMCID:PMC5216607

[6] Pant K,Peixoto E.Role of glucose metabolism reprogramming in the pathogenesis of cholangiocarcinoma.Front Med2020;7:113 PMCID:PMC7146077

[7] Ilyas SI.Pathogenesis, diagnosis, and management of cholangiocarcinoma.Gastroenterology2013;145:1215-29 PMCID:PMC3862291

[8] Pastore M,Gentilini A.Multifaceted aspects of metabolic plasticity in human cholangiocarcinoma: an overview of current perspectives.Cells2020;9:596 PMCID:PMC7140515

[9] Stenzinger A,Lehmann U.Molecular profiling in cholangiocarcinoma: a practical guide to next-generation sequencing.Cancer Treat Rev2024;122:102649

[10] Chen W,Liu Q,Wang Y.Unraveling the heterogeneity of cholangiocarcinoma and identifying biomarkers and therapeutic strategies with single-cell sequencing technology.Biomed Pharmacother2023;162:114697

[11] Carotenuto M,Forgione L.Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy.Explor Target Antitumor Ther2022;3:200-23 PMCID:PMC9400790

[12] Andraus W,de Meira Junior JD.Molecular profile of intrahepatic cholangiocarcinoma.Int J Mol Sci2023;25:461 PMCID:PMC10778975

[13] Porreca V,Corbella E.Unveil intrahepatic cholangiocarcinoma heterogeneity through the lens of omics and multi-omics approaches.Cancers2024;16:2889 PMCID:PMC11352949

[14] Lu M,Zhou Y.Long non-coding RNA LINC00665 promotes gemcitabine resistance of cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis.Cell Death Dis2021;12:72 PMCID:PMC7803957

[15] Elvevi A,Scaravaglio M.Clinical treatment of cholangiocarcinoma: an updated comprehensive review.Ann Hepatol2022;27:100737

[16] Valle J, Wasan H, Palmer DH, et al; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273-81.

[17] Srijiwangsa P,Na-Bangchang K.Effect of β-Eudesmol on NQO1 suppression-enhanced sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.BMC Pharmacol Toxicol2018;19:32 PMCID:PMC6006851

[18] Holohan C,Longley DB.Cancer drug resistance: an evolving paradigm.Nat Rev Cancer2013;13:714-26

[19] Hanahan D.Hallmarks of cancer: the next generation.Cell2011;144:646-74

[20] Park JH,Park HW.Cancer metabolism: phenotype, signaling and therapeutic targets.Cells2020;9:2308 PMCID:PMC7602974

[21] Vaupel P.Revisiting the Warburg effect: historical dogma versus current understanding.J Physiol2021;599:1745-57

[22] Zhang Y,Huang Z.Targeting glucose metabolism enzymes in cancer treatment: current and emerging strategies.Cancers2022;14:4568 PMCID:PMC9559313

[23] Zheng J.Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review).Oncol Lett2012;4:1151-7 PMCID:PMC3506713

[24] Xing F,Qin Y.The relationship of redox with hallmarks of cancer: the importance of homeostasis and context.Front Oncol2022;12:862743 PMCID:PMC9072740

[25] De Santis MC, Porporato PE, Martini M, Morandi A. Signaling pathways regulating redox balance in cancer metabolism.Front Oncol2018;8:126 PMCID:PMC5925761

[26] Thonsri U,Waraasawapati S.Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis.Histol Histopathol2017;32:503-10

[27] Kawada K,Sakai Y.Targeting metabolic reprogramming in KRAS-driven cancers.Int J Clin Oncol2017;22:651-9

[28] Ma Q,Wu K.The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy.Mol Cancer2025;24:14 PMCID:PMC11727292

[29] Zhang C,Liang Y.Tumour-associated mutant p53 drives the Warburg effect.Nat Commun2013;4:2935 PMCID:PMC3969270

[30] Gomes AS,Soares J.p53 and glucose metabolism: an orchestra to be directed in cancer therapy.Pharmacol Res2018;131:75-86

[31] Abukwaik R,Tennant D.p53 orchestrates cancer metabolism: unveiling strategies to reverse the Warburg effect.Bull Math Biol2024;86:124 PMCID:PMC11362376

[32] Li J,Tan Z.Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer.Theranostics2018;8:4050-61 PMCID:PMC6096397

[33] Parker SJ.Metabolic consequences of oncogenic IDH mutations.Pharmacol Ther2015;152:54-62 PMCID:PMC4489982

[34] Chan FF.Targeting the metabolic vulnerability of ARID1A-deficient hepatocellular carcinoma.Cell Mol Gastroenterol Hepatol2022;14:241-2 PMCID:PMC9254620

[35] Zhen Y,Shi L.FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma.Nat Commun2024;15:3805 PMCID:PMC11076599

[36] Holloway RW.Targeting mTOR and glycolysis in HER2-positive breast cancer.Cancers2021;13:2922 PMCID:PMC8230691

[37] Casak SJ,Fashoyin-Aje LA.FDA approval summary: ivosidenib for the treatment of patients with advanced unresectable or metastatic, chemotherapy refractory cholangiocarcinoma with an IDH1 mutation.Clin Cancer Res2022;28:2733-7 PMCID:PMC9250596

[38] Caligiuri A,Porro N.Oxidative stress and redox-dependent pathways in cholangiocarcinoma.Antioxidants2023;13:28 PMCID:PMC10812651

[39] Shestov AA,Ser Z.Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step.Elife2014;3:e03342 PMCID:PMC4118620

[40] Kinjo Y,Akiba J.SUOX and GLUT1 are biomarkers for the prognosis in large duct type intrahepatic cholangiocarcinoma.Hum Pathol2022;128:11-9

[41] Kozaka K,Takamura H.Differences in 18F-FDG uptake and expression of glucose transporter between 2 distinct subtypes of mass-forming intrahepatic cholangiocarcinomas.Clin Nucl Med2020;45:e267-73

[42] Kubo Y,Tanaka Y.Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma.Hum Pathol2014;45:1610-7

[43] Hao L,Peng Q,Deng J.Targeting glycolytic reprogramming in cholangiocarcinoma: a novel approach for metabolic therapy.J Inflamm Res2024;17:9665-81 PMCID:PMC11606715

[44] Szablewski L.Glucose transporters as markers of diagnosis and prognosis in cancer diseases.Oncol Rev2022;16:561 PMCID:PMC8941341

[45] Suwannakul N,Thanan R.Targeting fructose metabolism by glucose transporter 5 regulation in human cholangiocarcinoma.Genes Dis2022;9:1727-41 PMCID:PMC9485202

[46] Thamrongwaranggoon U,Seubwai W,Cha’on U.Aberrant GLUT1 expression is associated with carcinogenesis and progression of liver fluke-associated cholangiocarcinoma.In Vivo2021;35:267-74 PMCID:PMC7880799

[47] Luo XM,Fan J.Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma.J Int Med Res2010;38:1885-92

[48] Miller ZA,Mueller A.GLUT1 inhibitor BAY-876 induces apoptosis and enhances anti-cancer effects of bitter receptor agonists in head and neck squamous carcinoma cells.Cell Death Discov2024;10:339 PMCID:PMC11282258

[49] Adekola K,Shanmugam M.Glucose transporters in cancer metabolism.Curr Opin Oncol2012;24:650-4 PMCID:PMC6392426

[50] Thamrongwaranggoon U,Phoomak C.Targeting hexokinase II as a possible therapy for cholangiocarcinoma.Biochem Biophys Res Commun2017;484:409-15

[51] Raggi C,Rae C,Marra F.Metabolic reprogramming in cholangiocarcinoma.J Hepatol2022;77:849-64

[52] Peng M,Cao H.Dual FGFR and VEGFR inhibition synergistically restrain hexokinase 2-dependent lymphangiogenesis and immune escape in intrahepatic cholangiocarcinoma.J Gastroenterol2023;58:908-24 PMCID:PMC10423168

[53] Peng J,Li Y.PFKP is a prospective prognostic, diagnostic, immunological and drug sensitivity predictor across pan-cancer.Sci Rep2023;13:17399 PMCID:PMC10576092

[54] Fujiwara H,Misumi K.Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation.Sci Rep2019;9:18859 PMCID:PMC6906335

[55] Li X,Luo Y.Aldolase A enhances intrahepatic cholangiocarcinoma proliferation and invasion through promoting glycolysis.Int J Biol Sci2021;17:1782-94 PMCID:PMC8120471

[56] Yu G,Jin G.PKM2 regulates neural invasion of and predicts poor prognosis for human hilar cholangiocarcinoma.Mol Cancer2015;14:193 PMCID:PMC4650283

[57] Dang CV,Gao P.MYC-induced cancer cell energy metabolism and therapeutic opportunities.Clin Cancer Res2009;15:6479-83 PMCID:PMC2783410

[58] Qian Z,Lv Z.PKM2 upregulation promotes malignancy and indicates poor prognosis for intrahepatic cholangiocarcinoma.Clin Res Hepatol Gastroenterol2020;44:162-73

[59] Yu W,Xiao Y.Targeting PKM2 improves the gemcitabine sensitivity of intrahepatic cholangiocarcinoma cells via inhibiting β-catenin signaling pathway.Chem Biol Interact2024;387:110816

[60] Zhou Q,Yu M.GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism.Redox Biol2022;56:102458 PMCID:PMC9483790

[61] Chanda M,Ruangritchankul K,Cheepsunthorn CL.Inhibition of non-small cell lung cancer (NSCLC) proliferation through targeting G6PD.PeerJ2023;11:e16503 PMCID:PMC10704991

[62] Ghanem N,Araji K,Usta J.The pentose phosphate pathway in cancer: regulation and therapeutic opportunities.Chemotherapy2021;66:179-91

[63] Yang HC,Chiu DT.G6PD: A hub for metabolic reprogramming and redox signaling in cancer.Biomed J2021;44:285-92 PMCID:PMC8358196

[64] Nagashio R,Yanagita K.Prognostic significance of G6PD expression and localization in lung adenocarcinoma.Biochim Biophys Acta Proteins Proteom2019;1867:38-46

[65] Liu R,Tao B.Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance.Nat Commun2019;10:991 PMCID:PMC6397164

[66] Liu T,Wu H.Phosphogluconate dehydrogenase is a predictive biomarker for immunotherapy in hepatocellular carcinoma.Front Oncol2022;12:993503 PMCID:PMC9632284

[67] Ong AJ,Chi NHK.The positive feedback loop between Nrf2 and phosphogluconate dehydrogenase stimulates proliferation and clonogenicity of human hepatoma cells.Free Radic Res2020;54:906-17

[68] Zheng P,Zhou XH,Hu J.Glucose 6 phosphatase dehydrogenase (G6PD): a novel diagnosis marker related to gastrointestinal cancers.Am J Transl Res2023;15:4:2304-28 PMCID:PMC10182507

[69] Li R,Yang Y.Exploring the role of glucose6phosphate dehydrogenase in cancer (Review).Oncol Rep2020;44:2325-36

[70] Cao J,Zhang X.6PGD upregulation is associated with chemo- and immuno-resistance of renal cell carcinoma via AMPK signaling-dependent NADPH-mediated metabolic reprograming.Am J Med Sci2020;360:279-86

[71] Jin L.Crucial role of the pentose phosphate pathway in malignant tumors.Oncol Lett2019;17:4213-21 PMCID:PMC6444344

[72] Qiao J,Zhou H,Wu H.The pentose phosphate pathway: from mechanisms to implications for gastrointestinal cancers.Int J Mol Sci2025;26:610 PMCID:PMC11765532

[73] Li M,Yong H.Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation.Cell Death Dis2022;13:99 PMCID:PMC8810869

[74] Ying H,Lyssiotis CA.Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism.Cell2012;149:656-70 PMCID:PMC3472002

[75] Marbaniang C.Dysregulation of glucose metabolism by oncogenes and tumor suppressors in cancer cells.Asian Pac J Cancer Prev2018;19:2377-90 PMCID:PMC6249467

[76] He F,Wen T.NRF2, a transcription factor for stress response and beyond.Int J Mol Sci2020;21:4777 PMCID:PMC7369905

[77] Samatiwat P,Senggunprai L,Kukongviriyapan V.Nrf2 inhibition sensitizes cholangiocarcinoma cells to cytotoxic and antiproliferative activities of chemotherapeutic agents.Tumour Biol2016;37:11495-507

[78] Qu X,Shen L.Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS.PLoS One2017;12:e0173712 PMCID:PMC5354635

[79] Yu Y,Liu R,Feng H.Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: its implication for treatment.World J Surg Oncol2014;12:78 PMCID:PMC4230420

[80] Mathew M,Bhutia YD,Ganapathy V.Metabolic signature of Warburg effect in cancer: an effective and obligatory interplay between nutrient transporters and catabolic/anabolic pathways to promote tumor growth.Cancers2024;16:504 PMCID:PMC10854907

[81] Langhammer S,Hess-Stumpp H.LDH-A influences hypoxia-inducible factor 1α (HIF1 α) and is critical for growth of HT29 colon carcinoma cells in vivo.Target Oncol2011;6:155-62

[82] Liu D,Wu C.Prognostic significance of serum lactate dehydrogenase in patients with breast cancer: a meta-analysis.Cancer Manag Res2019;11:3611-9 PMCID:PMC6497911

[83] Malhotra G,Shinde RK,Nayak K.Significance of serum lactate dehydrogenase as a prognostic marker and outcome predictor in patients with breast cancer.Cureus2024;16:e55932 PMCID:PMC11004840

[84] Al-Khallaf H.Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight.Cell Biosci2017;7:37 PMCID:PMC5543436

[85] Rizzo A,Brandi G.IDH inhibitors in advanced cholangiocarcinoma: another arrow in the quiver?.Cancer Treat Res Commun2021;27:100356

[86] Fujii T,DiNardo CD,Janku F.Targeting isocitrate dehydrogenase (IDH) in cancer.Discov Med2016;21:117:373-80

[87] Gu Y,Yang Y.IDH1 mutation contributes to myeloid dysplasia in mice by disturbing heme biosynthesis and erythropoiesis.Blood2021;137:945-58

[88] Xiang X,Zhang C.IDH mutation subgroup status associates with intratumor heterogeneity and the tumor microenvironment in intrahepatic cholangiocarcinoma.Adv Sci2021;8:e2101230 PMCID:PMC8425914

[89] Feichtinger RG,Kemmerling R,Kiesslich T.Low VDAC1 expression is associated with an aggressive phenotype and reduced overall patient survival in cholangiocellular carcinoma.Cells2019;8:539 PMCID:PMC6627691

[90] Ashton TM,Kunz-Schughart LA.Oxidative phosphorylation as an emerging target in cancer therapy.Clin Cancer Res2018;24:2482-90

[91] Kulthawatsiri T,Phetcharaburanin J.Metabolomic analyses uncover an inhibitory effect of niclosamide on mitochondrial membrane potential in cholangiocarcinoma cells.PeerJ2023;11:e16512 PMCID:PMC10676079

[92] Bonuccelli G,Whitaker-Menezes D.Ketones and lactate “fuel” tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism.Cell Cycle2010;9:3506-14 PMCID:PMC3047616

[93] Pavlides S,Castello-Cros R.The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.Cell Cycle2009;8:3984-4001

[94] Raggi C,Sacco E.Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma.J Hepatol2021;74:1373-85

[95] Sancho P,Tavera A.MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells.Cell Metab2015;22:590-605

[96] Zhao Z,Wang Z.The effect of oxidative phosphorylation on cancer drug resistance.Cancers2022;15:62 PMCID:PMC9817696

[97] Ghoneum A,Warren BO,Said N.Redox homeostasis and metabolism in cancer: a complex mechanism and potential targeted therapeutics.Int J Mol Sci2020;21:3100 PMCID:PMC7247161

[98] Mcbeth C.Redox in cancer metabolism: manipulation of cancer metabolism through exploitation of redox environments.ChemElectroChem2023;10:e202300117

[99] Patra KC.The pentose phosphate pathway and cancer.Trends Biochem Sci2014;39:347-54 PMCID:PMC4329227

[100] Yang M,Lyu Z.Implication of ferroptosis in cholangiocarcinoma: a potential future target?.Cancer Manag Res2023;15:335-42 PMCID:PMC10093512

[101] Luo J.KRAS mutation in pancreatic cancer.Semin Oncol2021;48:10-8 PMCID:PMC8380752

[102] Zhu G,Xia H,Bi F.Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer.Mol Cancer2021;20:143 PMCID:PMC8571891

[103] Luo J,Pellini B.Overcoming KRAS-mutant lung cancer.Am Soc Clin Oncol Educ Book2022;42:1-11

[104] Moffat GT,Meric-Bernstam F.KRAS allelic variants in biliary tract cancers.JAMA Netw Open2024;7:e249840 PMCID:PMC11074811

[105] Zhou SL,Sun RQ.Association of KRAS variant subtypes with survival and recurrence in patients with surgically treated intrahepatic cholangiocarcinoma.JAMA Surg2022;157:59-65 PMCID:PMC8567187

[106] Huang L,Wang F.KRAS mutation: from undruggable to druggable in cancer.Signal Transduct Target Ther2021;6:386 PMCID:PMC8591115

[107] Fell JB,Baer BR.Identification of the clinical development candidate MRTX849, a covalent KRAS^G12C inhibitor for the treatment of cancer.J Med Chem2020;63:6679-93

[108] Ostrem JM,Sos ML,Shokat KM.K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions.Nature2013;503:548-51 PMCID:PMC4274051

[109] Mukhopadhyay S,McCormick F.The metabolic landscape of RAS-driven cancers from biology to therapy.Nat Cancer2021;2:271-83 PMCID:PMC8045781

[110] Yun J,Cheong I.Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.Science2009;325:1555-9 PMCID:PMC2820374

[111] Liu J,Kattan WE.Glycolysis regulates KRAS plasma membrane localization and function through defined glycosphingolipids.Nat Commun2023;14:465 PMCID:PMC9884228

[112] Patra KC,Bhaskar PT.Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer.Cancer Cell2013;24:213-28 PMCID:PMC3753022

[113] Guo C,Yu Y.TP53 /KRAS co-mutations create divergent prognosis signatures in intrahepatic cholangiocarcinoma.Front Genet2022;13:844800 PMCID:PMC8990229

[114] Harami-Papp H,Munkácsy G.TP53 mutation hits energy metabolism and increases glycolysis in breast cancer.Oncotarget2016;7:67183-95 PMCID:PMC5341867

[115] Madan E,Bhatt M,Kuppusamy P.Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor.Oncotarget2011;2:948-57 PMCID:PMC3282098

[116] Boidot R,Meulle A.Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors.Cancer Res2012;72:939-48

[117] Kawauchi K,Tobiume K.p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation.Nat Cell Biol2008;10:611-8

[118] Contractor T.p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2.Cancer Res2012;72:560-7

[119] Hu W,Wu R,Levine A.Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function.Proc Natl Acad Sci U S A2010;107:7455-60 PMCID:PMC2867677

[120] Suzuki S,Poyurovsky MV.Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species.Proc Natl Acad Sci U S A2010;107:7461-6 PMCID:PMC2867754

[121] Puzio-Kuter AM.The role of p53 in metabolic regulation.Genes Cancer2011;2:385-91 PMCID:PMC3135642

[122] Liu J,Hu W.Tumor suppressor p53 and metabolism.J Mol Cell Biol2019;11:284-92 PMCID:PMC6487777

[123] Jiang P,Wang X.p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase.Nat Cell Biol2011;13:310-6 PMCID:PMC3110666

[124] Salati M,Baldessari C.IDH signalling pathway in cholangiocarcinoma: from biological rationale to therapeutic targeting.Cancers2020;12:3310 PMCID:PMC7696955

[125] Ntanasis-Stathopoulos I,Gavriatopoulou M,Pawlik TM.Cholangiocarcinoma: investigations into pathway-targeted therapies.Expert Rev Anticancer Ther2020;20:765-73

[126] Bralten LB,Balvers R.IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo.Ann Neurol2011;69:455-63

[127] Birner P,Christov C.Mutant IDH1 inhibits PI3K/Akt signaling in human glioma.Cancer2014;120:2440-7

[128] Cheng T,Yang C.Pyruvate carboxylase is required for glutamine-independent growth of tumor cells.Proc Natl Acad Sci U S A2011;108:8674-9 PMCID:PMC3102381

[129] Du D,Qin M.Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma.Acta Pharm Sin B2022;12:558-80 PMCID:PMC8897153

[130] Abou-Alfa GK,Javle MM.Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.Lancet Oncol2020;21:796-807 PMCID:PMC7523268

[131] Jiang Z,Lu X.The role of dysregulated metabolism and associated genes in gastric cancer initiation and development.Transl Cancer Res2024;13:3854-68 PMCID:PMC11319955

[132] Kuo TL,Chen LT.ARID1A loss in pancreas leads to islet developmental defect and metabolic disturbance.iScience2023;26:105881 PMCID:PMC9840936

[133] Guo B,Alexander W.Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma.Cell Rep2022;40:111253 PMCID:PMC9808599

[134] Zhao S,Wu W.ARID1A variations in cholangiocarcinoma: clinical significances and molecular mechanisms.Front Oncol2021;11:693295 PMCID:PMC8267411

[135] Xing T,Chen Y.Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma.Cell Rep Med2023;4:101264 PMCID:PMC10694624

[136] Zhang FK,Wang K.Targeting USP9X-AMPK axis in ARID1A-deficient hepatocellular carcinoma.Cell Mol Gastroenterol Hepatol2022;14:101-27 PMCID:PMC9117818

[137] Farshidfar F, Zheng S, Gingras MC, et al; Cancer Genome Atlas Network. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles. Cell Rep. 2017;18:2780-94. PMCID:PMC5493145

[138] Goyal L, Meric-Bernstam F, Hollebecque A, et al; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023;388:228-39.

[139] Goyal L,Crolley VE.Targeting FGFR inhibition in cholangiocarcinoma.Cancer Treat Rev2021;95:102170

[140] Ayasun R,Sahin I.The role of HER2 status in the biliary tract cancers.Cancers2023;15:2628 PMCID:PMC10177412

[141] Saengboonmee C,Pairojkul C.High glucose enhances progression of cholangiocarcinoma cells via STAT3 activation.Sci Rep2016;6:18995 PMCID:PMC4705543

[142] Thonsri U,Wongkham C.High glucose-ROS conditions enhance the progression in cholangiocarcinoma via upregulation of MAN2A2 and CHD8.Cancer Sci2021;112:254-64 PMCID:PMC7780024

[143] Saengboonmee C,Supabphol S.NF-κB and STAT3 co-operation enhances high glucose induced aggressiveness of cholangiocarcinoma cells.Life Sci2020;262:118548 PMCID:PMC7686287

[144] Liu C,Fan Z.The mechanism of warburg effect-induced chemoresistance in cancer.Front Oncol2021;11:698023 PMCID:PMC8446599

[145] Yothaisong S,Techasen A.Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy.Tumour Biol2013;34:3637-48

[146] Phoomak C,Silsirivanit A.High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation.Sci Rep2017;7:43842 PMCID:PMC5338328

[147] Detarya M,Seubwai W.High glucose upregulates FOXM1 expression via EGFR/STAT3 dependent activation to promote progression of cholangiocarcinoma.Life Sci2021;271:119114

[148] Colyn L,Latasa MU.New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.J Exp Clin Cancer Res2022;41:183 PMCID:PMC9134609

[149] Fujinaga A,Hirashita Y.Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma.BMC Gastroenterol2023;23:157 PMCID:PMC10190040

[150] Li L,Qiu Z.Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway.Phytomedicine2023;109:154575

[151] Salamanca-Cardona L,Poot AJ.In vivo imaging of glutamine metabolism to the oncometabolite 2-hydroxyglutarate in IDH1/2 mutant tumors.Cell Metab2017;26:830-41.e3 PMCID:PMC5718944

[152] Gonsalves WI,Hitosugi T.Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies.JCI Insight2018;3:94543 PMCID:PMC5821206

[153] Thomas T,Young R.Imaging 2-hydroxyglutarate and other brain oncometabolites pertinent to critical genomic alterations in brain tumors.BJR Open2023;5:20210070 PMCID:PMC10077413

[154] Rimini M,Fabregat-Franco C.Next-generation sequencing analysis of cholangiocarcinoma identifies distinct IDH1-mutated clusters.Eur J Cancer2022;175:299-310

[155] Kaewpitoon SJ,Rujirakul R.Benefits of metformin use for cholangiocarcinoma.Asian Pac J Cancer Prev2015;16:8079-83

[156] Jiang X,Wang D.Metformin inhibits tumor growth by regulating multiple miRNAs in human cholangiocarcinoma.Oncotarget2015;6:3178-94 PMCID:PMC4413646

[157] Molenaar RJ,Khurshed M.Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours.BMJ Open2017;7:e014961 PMCID:PMC5541450

[158] Dutka M,Francuz T.SGLT-2 inhibitors in cancer treatment-mechanisms of action and emerging new perspectives.Cancers2022;14:5811 PMCID:PMC9738342

[159] Kaji K,Seki K.Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake.Int J Cancer2018;142:1712-22

[160] Scheen AJ.Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus.Drugs2015;75:33-59

[161] Xu D,Xie X.Inhibitory effects of canagliflozin on pancreatic cancer are mediated via the downregulation of glucose transporter1 and lactate dehydrogenase A.Int J Oncol2020;57:1223-33

[162] Taguchi D,Sakai H.Dual roles of canagliflozin on cholangiocarcinoma cell growth and enhanced growth suppression in combination with FK866.Int J Mol Sci2025;26:978 PMCID:PMC11817608

[163] Lee YH,Fang X.JNK-mediated Ser27 phosphorylation and stabilization of SIRT1 promote growth and progression of colon cancer through deacetylation-dependent activation of Snail.Mol Oncol2022;16:1555-71 PMCID:PMC8978515

[164] Yu XJ,Li C.SIRT1-ZEB1-positive feedback promotes epithelial-mesenchymal transition process and metastasis of osteosarcoma.J Cell Biochem2019;120:3727-35

[165] Hayashi M,Harada S.GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells.BMC Cancer2025;25:716 PMCID:PMC12004878

[166] Liu Y,Zhang W.A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo.Mol Cancer Ther2012;11:1672-82

[167] Li YL,Hsu JL,Guh JH.The combination of MK-2206 and WZB117 exerts a synergistic cytotoxic effect against breast cancer cells.Front Pharmacol2019;10:1311 PMCID:PMC6856645

[168] Schmidl S,Iancu CV,Oprea TI.Identification of new GLUT2-selective inhibitors through in silico ligand screening and validation in eukaryotic expression systems.Sci Rep2021;11:13751 PMCID:PMC8253845

[169] Silvestrini B,Cioli V.Effects of lonidamine alone or combined with hyperthermia in some experimental cell and tumour systems.Br J Cancer1983;47:221-31 PMCID:PMC2011275

[170] Morais-Santos F,Pinheiro S.Differential sensitivities to lactate transport inhibitors of breast cancer cell lines.Endocr Relat Cancer2014;21:27-38

[171] Lee GH,Kim HR.Monoamine carboxylate transporters are involved in BI-1-associated cancer metastasis in HT1080 colon fibrosarcoma cells.Int J Oncol2011;39:209-16

[172] Guo L,Worth AJ.Inhibition of mitochondrial complex II by the anticancer agent lonidamine.J Biol Chem2016;291:42-57 PMCID:PMC4697178

[173] Nancolas B,Zhou R.The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters.Biochem J2016;473:929-36 PMCID:PMC4814305

[174] Carapella CM,Cattani F.The potential role of lonidamine (LND) in the treatment of malignant glioma. Phase II study.J Neurooncol1989;7:103-8

[175] De Lena M,Latorre A.Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study.Eur J Cancer2001;37:364-8

[176] Kobayashi H,Nishimura H,Harada H.RNAi screening reveals a synthetic chemical-genetic interaction between ATP synthase and PFK1 in cancer cells.Cancer Sci2023;114:1663-71 PMCID:PMC10067418

[177] Chen F,Cordes T.The yin and yang of itaconate metabolism and its impact on the tumor microenvironment.Curr Opin Biotechnol2023;84:102996

[178] Wang Y,Liu Y.Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma.iScience2024;27:110725 PMCID:PMC11388021

[179] Thonsri U,Waraasawapati S.Antitumor effect of shikonin, a PKM2 inhibitor, in cholangiocarcinoma cell lines.Anticancer Res2020;40:5115-24

[180] Liu C,Li K.Shikonin inhibits cholangiocarcinoma cell line QBC939 by regulating apoptosis, proliferation, and invasion.Cell Transplant2021;30:963689720979162 PMCID:PMC7863558

[181] Zhou G,Wang X,Zhou Y.TRAIL enhances shikonin induced apoptosis through ROS/JNK signaling in cholangiocarcinoma cells.Cell Physiol Biochem2017;42:1073-86

[182] Kim DJ,Kang MG.Pyruvate kinase isoenzyme M2 is a therapeutic target of gemcitabine-resistant pancreatic cancer cells.Exp Cell Res2015;336:119-29

[183] Wang Y,Nan Y.PKM2 inhibitor shikonin overcomes the cisplatin resistance in bladder cancer by inducing necroptosis.Int J Biol Sci2018;14:1883-91 PMCID:PMC6231221

[184] Su Q,Tan Q.The role of pyruvate kinase M2 in anticancer therapeutic treatments.Oncol Lett2019;18:5663-72 PMCID:PMC6865080

[185] Ning X,Li R,McNutt MA.Synthesis and antitumor activity of novel 2, 3-didithiocarbamate substituted naphthoquinones as inhibitors of pyruvate kinase M2 isoform.J Enzyme Inhib Med Chem2018;33:126-9 PMCID:PMC6010099

[186] Lu W,Zhang Y.Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer.Sci Rep2016;6:26351 PMCID:PMC4901292

[187] Ning X,Li R.Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase.Eur J Med Chem2017;138:343-52

[188] An Y,Li L.Micheliolide derivative DMAMCL inhibits glioma cell growth in vitro and in vivo.PLoS One2015;10:e0116202 PMCID:PMC4320118

[189] Ji Q,Sun Y.Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells.Oncotarget2016;7:65012-23 PMCID:PMC5323134

[190] Shang D,Guo L,Liu L.Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2.Int J Oncol2017;50:1848-56

[191] Zhou Y,Su J.Benserazide is a novel inhibitor targeting PKM2 for melanoma treatment.Int J Cancer2020;147:139-51

[192] Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication.Biochem J2018;475:1611-34 PMCID:PMC5941316

[193] Li W,Wu S.Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2.J Exp Clin Cancer Res2017;36:58 PMCID:PMC5399312

[194] Schwartz AG.Dehydroepiandrosterone, cancer, and aging.Aging Dis2022;13:423-32 PMCID:PMC8947821

[195] Kilanczyk E,Banales JM,Milkiewicz M.DHEA protects human cholangiocytes and hepatocytes against apoptosis and oxidative stress.Cells2022;11:1038 PMCID:PMC8947473

[196] Qin L,Yang F.Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma.PLoS One2022;17:e0260180 PMCID:PMC8812988

[197] Mele L,Papaccio F.A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo.Cell Death Dis2018;9:572 PMCID:PMC5951921

[198] De Maria S,Lombardi A.Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell.J Transl Med2013;11:264 PMCID:PMC3854516

[199] Indraccolo U,Mignini F.Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis.Ann Ist Super Sanita2017;53:125-34

[200] Chen H,Bao L.6PGD inhibition sensitizes hepatocellular carcinoma to chemotherapy via AMPK activation and metabolic reprogramming.Biomed Pharmacother2019;111:1353-8

[201] Lin R,Shan C.6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.Nat Cell Biol2015;17:1484-96 PMCID:PMC4628560

[202] Mihaylova MM.The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.Nat Cell Biol2011;13:1016-23 PMCID:PMC3249400

[203] Xu IM,Lin SH.Transketolase counteracts oxidative stress to drive cancer development.Proc Natl Acad Sci U S A2016;113:E725-34 PMCID:PMC4760787

[204] Kowalik MA,Perra A.Emerging role of the pentose phosphate pathway in hepatocellular carcinoma.Front Oncol2017;7:87 PMCID:PMC5425478

[205] Mariadasse R,Jayaprakash P.Mechanical insights of oxythiamine compound as potent inhibitor for human transketolase-like protein 1 (TKTL1 protein).J Recept Signal Transduct Res2016;36:233-42

[206] Raïs B,Puigjaner J.Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich’s tumor cells through inhibition of the pentose cycle.FEBS Lett1999;456:113-8

[207] Zhang H,Lee WN.Inhibition of protein phosphorylation in MIA pancreatic cancer cells: confluence of metabolic and signaling pathways.J Proteome Res2010;9:980-9 PMCID:PMC2836017

[208] Yang CM,Liao JW.The in vitro and in vivo anti-metastatic efficacy of oxythiamine and the possible mechanisms of action.Clin Exp Metastasis2010;27:341-9

[209] Wang CY,Chang TC.Dual effects for lovastatin in anaplastic thyroid cancer: the pivotal effect of transketolase (TKT) on lovastatin and tumor proliferation.J Investig Med2018;66:1-9

[210] Liu CL,Lee JJ.Targeting the pentose phosphate pathway increases reactive oxygen species and induces apoptosis in thyroid cancer cells.Mol Cell Endocrinol2020;499:110595

[211] Boros LG,Lim S.Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth.Pancreas2001;22:1-7

[212] Li S,Dai W.Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.Br J Cancer2017;117:1518-28 PMCID:PMC5680469

[213] Lachaise F,Drougard C.Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient xeroderma pigmentosum fibroblasts and SV40-transformed human cells.Free Radic Biol Med2001;30:1365-73

[214] Ogawa T,Yoshino M.Inhibition by fructose 1,6-bisphosphate of transaldolase from Escherichia coli.FEMS Microbiol Lett2016;363:fnw183

[215] Verma S,Serganova I.Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models.J Clin Invest2024;134:e177606 PMCID:PMC11364391

[216] Boudreau A,Hitz A.Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition.Nat Chem Biol2016;12:779-86

[217] Xiao Y,Xu Y.Emerging therapies in cancer metabolism.Cell Metab2023;35:1283-303

[218] Doherty JR.Targeting lactate metabolism for cancer therapeutics.J Clin Invest2013;123:3685-92 PMCID:PMC3754272

[219] Buck MD,Kaech SM.Metabolic instruction of immunity.Cell2017;169:570-86 PMCID:PMC5648021

[220] O’Neill LA,Rathmell J.A guide to immunometabolism for immunologists.Nat Rev Immunol2016;16:553-65 PMCID:PMC5001910

[221] Xu K,Peng M.Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity.Science2021;371:405-10 PMCID:PMC8380312

[222] Le A,Gouw AM.Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression.Proc Natl Acad Sci U S A2010;107:2037-42 PMCID:PMC2836706

[223] Ooi AT.Molecular pathways: targeting cellular energy metabolism in cancer via inhibition of SLC2A1 and LDHA.Clin Cancer Res2015;21:2440-4 PMCID:PMC4452440

[224] Granchi C,Giacomelli C.Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells.J Med Chem2011;54:1599-612

[225] Manerba M,Fiume L.Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase.ChemMedChem2012;7:311-7

[226] Zhao Y,Liu Z.Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism.Cancer Res2011;71:4585-97 PMCID:PMC3129363

[227] Zhou M,Ding Y.Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol.Mol Cancer2010;9:33 PMCID:PMC2829492

[228] Seth P,Tang J.On-target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate.Neoplasia2011;13:60-71 PMCID:PMC3022429

[229] Zhu AX,Javle MM.Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial.JAMA Oncol2021;7:1669-77 PMCID:PMC8461552

[230] Lamarca A, Palmer DH, Wasan HS, et al; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22:690-701. PMCID:PMC8082275

[231] Yoo C,Jeong JH.Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study.Lancet Oncol2021;22:1560-72

[232] Vogel A, Bridgewater J, Edeline J, et al; ESMO Guidelines Committee. Electronic address: [e-mail]. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:127-40.

[233] Rodon J,Mercade TM.Abstract CT098: a first-in-human phase 1 study of LY3410738, a covalent inhibitor of mutant IDH, in advanced IDH-mutant cholangiocarcinoma and other solid tumors.Cancer Research2023;83:CT098-CT098

[234] Li Y,Zhang Y,Song Y.Advances in targeted therapy of cholangiocarcinoma.Ann Med2024;56:2310196 PMCID:PMC10877652

[235] Saha SK,Kleinstiver BP.Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC dependence in intrahepatic cholangiocarcinoma.Cancer Discov2016;6:727-39 PMCID:PMC5458737

[236] Fathi AT,Faramand R.Biochemical, epigenetic, and metabolic approaches to target IDH mutations in acute myeloid leukemia.Semin Hematol2015;52:165-71

[237] Yang SM,Lee JY,Lee JM.Regulation of glucose and glutamine metabolism to overcome cisplatin resistance in intrahepatic cholangiocarcinoma.BMB Rep2023;56:600-5 PMCID:PMC10689087

[238] Mohan A,Wuchu F.Devimistat in combination with gemcitabine and cisplatin in biliary tract cancer: preclinical evaluation and phase Ib multicenter clinical trial (BilT-04).Clin Cancer Res2023;29:2394-400 PMCID:PMC10330233

[239] Russell DA,Serreli R.Hydroxylated rotenoids selectively inhibit the proliferation of prostate cancer cells.J Nat Prod2020;83:1829-45 PMCID:PMC7611836

[240] Cadassou O.OXPHOS inhibitors, metabolism and targeted therapies in cancer.Biochem Pharmacol2023;211:115531

[241] Rha SY,Shin YG.Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors.JCO2020;38:3590

[242] Ellinghaus P,Unterschemmann K.BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I.Cancer Med2013;2:611-24 PMCID:PMC3892793

[243] Molina JR,Protopopova M.An inhibitor of oxidative phosphorylation exploits cancer vulnerability.Nat Med2018;24:1036-46

[244] Yap TA,Mahendra M.Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.Nat Med2023;29:115-26 PMCID:PMC11975418

[245] Bordt EA,Roelofs BA.The putative drp1 inhibitor mdivi-1 is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species.Dev Cell2017;40:583-94.e6 PMCID:PMC5398851

[246] Bastian A,Humphries KM.AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization.Cancer Lett2017;388:149-57 PMCID:PMC5318233

[247] Bastian A,Disch BC.A small molecule with anticancer and antimetastatic activities induces rapid mitochondrial-associated necrosis in breast cancer.J Pharmacol Exp Ther2015;353:392-404 PMCID:PMC4407723

[248] Bekaii-saab TS,Yaeger R.KRYSTAL-1: updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRAS^G12C mutation.JCO2022;40:519

[249] Shelton F,Trinh D.Abstract 4448: effects of adagrasib on cholesterol, lipid and glucose gene expression regulation in tumor xenograft models and patient samples.Cancer Research2024;84:4448

[250] FDA approves first KRAS inhibitor: sotorasib. Cancer Discov. 2021;11:OF4.

[251] Hong DS,Strickler JH.KRAS^G12C inhibition with sotorasib in advanced solid tumors.N Engl J Med2020;383:1207-17 PMCID:PMC7571518

[252] Janku F,Fujii T.Multiplex KRASG12/G13 mutation testing of unamplified cell-free DNA from the plasma of patients with advanced cancers using droplet digital polymerase chain reaction.Ann Oncol2017;28:642-50 PMCID:PMC5834133

[253] Thongyoo P,Aphivatanasiri C.KRAS mutations in cholangiocarcinoma: prevalence, prognostic value, and KRAS G12/G13 detection in cell-free DNA.Cancer Genomics Proteomics2025;22:112-26 PMCID:PMC11696325

[254] Zhang ZR,Ji Y.Sotorasib inhibits ubiquitination degradation of TXNIP and suppresses glucose metabolism in KRAS^G12C mutant bladder cancer.Am J Cancer Res2024;14:5251-68 PMCID:PMC11626273

[255] Nishikawa S.Drugs targeting p53 mutations with FDA approval and in clinical trials.Cancers2023;15:429 PMCID:PMC9856662

[256] Bykov VJ,Zhang M,Abrahmsen L.Targeting of mutant p53 and the cellular redox balance by APR-246 as a strategy for efficient cancer therapy.Front Oncol2016;6:21 PMCID:PMC4737887

[257] Liu M,Qin Y.Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer.Exp Hematol Oncol2020;9:179

[258] Mishra A,DeZern AE.Eprenetapopt plus azacitidine after allogeneic hematopoietic stem-cell transplantation for TP53-mutant acute myeloid leukemia and myelodysplastic syndromes.J Clin Oncol2022;40:3985-93

[259] Sallman DA,Garcia-Manero G.Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes.J Clin Oncol2021;39:1584-94 PMCID:PMC8099410

[260] Aggarwal M,Sinclair E.Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth.Cell Death Differ2016;23:1615-27 PMCID:PMC5041190

[261] Davison K,Miller WH Jr.Arsenic trioxide: mechanisms of action.Semin Hematol2002;39:3-7

[262] Yedjou C,Jenkins J.Basic mechanisms of arsenic trioxide (ATO)-induced apoptosis in human leukemia (HL-60) cells.J Hematol Oncol2010;3:28 PMCID:PMC2939535

[263] Chen S,Liang Y.Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site.Cancer Cell2021;39:225-39.e8

[264] Yan W,Zhang Y.Arsenic trioxide reactivates proteasome-dependent degradation of mutant p53 protein in cancer cells in part via enhanced expression of Pirh2 E3 ligase.PLoS One2014;9:e103497 PMCID:PMC4130519

[265] Wen J,Wang Z.Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies.Front Pharmacol2025;16:1536388 PMCID:PMC11882591

[266] Terzian T,Iwakuma T.The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss.Genes Dev2008;22:1337-44 PMCID:PMC2377188

[267] Alexandrova EM,Li D.Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment.Nature2015;523:352-6 PMCID:PMC4506213

[268] Lukashchuk N.Ubiquitination and degradation of mutant p53.Mol Cell Biol2007;27:8284-95 PMCID:PMC2169174

[269] Kudryavtsev VA,Mosina VA,Kabakov AE.Induction of Hsp70 in tumor cells treated with inhibitors of the Hsp90 activity: a predictive marker and promising target for radiosensitization.PLoS One2017;12:e0173640 PMCID:PMC5349677

[270] Concin N,Combe P.Phase II results of GANNET53: a European multicenter phase I/randomized II trial of the Hsp90 inhibitor Ganetespib (G) combined with weekly Paclitaxel (P) in women with high-grade serous, high-grade endometrioid, or undifferentiated, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.JCO2018;36:5567 PMCID:PMC10824373

[271] Ray-Coquard I,Berger R.Part I of GANNET53: a European multicenter phase I/II trial of the Hsp90 inhibitor ganetespib combined with weekly paclitaxel in women with high-grade, platinum-resistant epithelial ovarian cancer-a study of the GANNET53 consortium.Front Oncol2019;9:832 PMCID:PMC6746955

[272] Jiang W,He XR,He XY.Statins: a repurposed drug to fight cancer.J Exp Clin Cancer Res2021;40:241 PMCID:PMC8306262

[273] Mehibel M,Voelxen N.Statin-induced metabolic reprogramming in head and neck cancer: a biomarker for targeting monocarboxylate transporters.Sci Rep2018;8:16804 PMCID:PMC6235971

[274] Parrales A,Iyer SV.DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway.Nat Cell Biol2016;18:1233-43 PMCID:PMC5340314

[275] Ingallina E,Bertolio R.Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis.Nat Cell Biol2018;20:28-35 PMCID:PMC6179142

[276] Gray RT,Bankhead P.Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study.Br J Cancer2017;116:1652-9 PMCID:PMC5518863

[277] Nishikawa S,Takahashi K.Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection.Cancer Manag Res2019;11:3419-32 PMCID:PMC6497483

[278] Foggetti G,Russo D.Autophagy induced by SAHA affects mutant P53 degradation and cancer cell survival.Biosci Rep2019;39:BSR20181345 PMCID:PMC6379511

[279] Li D,Moll UM.SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis.Cell Death Differ2011;18:1904-13 PMCID:PMC3170683

[280] Li D,Schulz R.Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells.Mol Cancer Res2011;9:577-88 PMCID:PMC3097033

[281] Topatana W,Li S.Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation.J Hematol Oncol2020;13:118 PMCID:PMC7470446

[282] Wang X.Identification of potential synthetic lethal genes to p53 using a computational biology approach.BMC Med Genomics2013;6:30 PMCID:PMC3847148

[283] Wu CE,Yeh CN.Targeting P53 as a future strategy to overcome gemcitabine resistance in biliary tract cancers.Biomolecules2020;10:1474 PMCID:PMC7690712

[284] Hirai H,Okada M.MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil.Cancer Biol Ther2010;9:514-22

[285] Leijen S,Sonke GS.Phase II study of WEE1 inhibitor AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months.J Clin Oncol2016;34:4354-61

[286] Moore KN,Hamilton EP.Adavosertib with chemotherapy in patients with primary platinum-resistant ovarian, fallopian tube, or peritoneal cancer: an open-label, four-arm, phase II study.Clin Cancer Res2022;28:36-44

[287] Oza AM,Grischke EM.A biomarker-enriched, randomized phase II trial of adavosertib (AZD1775) plus paclitaxel and carboplatin for women with platinum-sensitive TP53-mutant ovarian cancer.Clin Cancer Res2020;26:4767-76

[288] Seligmann JF, Fisher DJ, Brown LC, et al; FOCUS4 Trial Investigators. Inhibition of WEE1 is effective in TP53- and RAS-mutant metastatic colorectal cancer: a randomized trial (FOCUS4-C) comparing adavosertib (AZD1775) with active monitoring. J Clin Oncol. 2021;39:3705-15. PMCID:PMC8601321

[289] Liu JF,Campos SM.Phase II study of the WEE1 inhibitor adavosertib in recurrent uterine serous carcinoma.J Clin Oncol2021;39:1531-9

[290] McKerrow W,Mendez-Dorantes C.LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.Proc Natl Acad Sci U S A2022;119:e2115999119 PMCID:PMC8872788

[291] Tiwari B,Caillet CJ,Royer SK.p53 directly represses human LINE1 transposons.Genes Dev2020;34:1439-51 PMCID:PMC7608743

[292] Wylie A,D’Brot A.p53 genes function to restrain mobile elements.Genes Dev2016;30:64-77 PMCID:PMC4701979

[293] Rajurkar M,Solovyov A.Reverse transcriptase inhibition disrupts repeat element life cycle in colorectal cancer.Cancer Discov2022;12:1462-81 PMCID:PMC9167735

[294] Di Agostino S,Ingallina E.YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins.EMBO Rep2016;17:188-201 PMCID:PMC5290815

[295] Mo JS,Gong R,Guan KL.Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs).Genes Dev2012;26:2138-43 PMCID:PMC3465735

[296] Göbel A,Browne AJ.Combined inhibition of the mevalonate pathway with statins and zoledronic acid potentiates their anti-tumor effects in human breast cancer cells.Cancer Lett2016;375:162-71

[297] Schmidmaier R,Baumann P,Meinhardt G.Synergistic antimyeloma effects of zoledronate and simvastatin.Anticancer Drugs2006;17:621-9

[298] Sorrentino G,Specchia V.Metabolic control of YAP and TAZ by the mevalonate pathway.Nat Cell Biol2014;16:357-66

[299] Xu S.The role of ARID1A in tumors: tumor initiation or tumor suppression?.Front Oncol2021;11:745187 PMCID:PMC12183088

[300] Pant K,Richard S.Role of histone deacetylases in carcinogenesis: potential role in cholangiocarcinoma.Cells2020;9:780 PMCID:PMC7140894

[301] Zhang X,Jiao Y,Yang Q.PHGDH Inhibitor CBR-5884 inhibits epithelial ovarian cancer progression via ROS/Wnt/β-catenin pathway and plays a synergistic role with PARP inhibitor olaparib.Oxid Med Cell Longev2022;2022:9029544 PMCID:PMC9467758

[302] Chen J,Huang Y.EZH2 mediated metabolic rewiring promotes tumor growth independently of histone methyltransferase activity in ovarian cancer.Mol Cancer2023;22:85 PMCID:PMC10199584

[303] Liu Y,Guo X.Tumor-suppressive function of EZH2 is through inhibiting glutaminase.Cell Death Dis2021;12:975 PMCID:PMC8528894

[304] Roskoski R Jr.Properties of FDA-approved small molecule protein kinase inhibitors: a 2023 update.Pharmacol Res2023;187:106552

[305] Goyal L,Liu LY.TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma.Cancer Discov2019;9:1064-79 PMCID:PMC6677584

[306] Abou-Alfa GK,Hollebecque A.Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study.Lancet Oncol2020;21:671-84 PMCID:PMC8461541

[307] Javle M,Azad NS.Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study.Lancet Oncol2021;22:1290-300

[308] Ohba A,Kawamoto Y.Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase II trial.J Clin Oncol2024;42:3207-17 PMCID:PMC11404765

[309] Ohba A,Kawamoto Y.Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): an investigator-initiated multicenter phase 2 study (HERB trial).JCO2022;40:4006

[310] Meric-bernstam F,Oaknin A.Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results.JCO2023;41:LBA3000

[311] Harding JJ, Fan J, Oh DY, et al; HERIZON-BTC-01 study group. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24:772-82.

[312] Meric-Bernstam F,Hamilton E.Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study.Lancet Oncol2022;23:1558-70

[313] Harding JJ,Shah RH.Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers.Nat Commun2023;14:630 PMCID:PMC9902444

[314] Nakamura Y,Sunakawa Y.Tucatinib and trastuzumab for previously treated HER2-positive metastatic biliary tract cancer (SGNTUC-019): a phase 2 basket study.JCO2023;41:4007

[315] Lee CK,Cheon J.Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14).Lancet Gastroenterol Hepatol2023;8:56-65

[316] Ostwal V,Bhargava P.Trastuzumab plus gemcitabine-cisplatin for treatment-naïve human epidermal growth factor receptor 2-positive biliary tract adenocarcinoma: a multicenter, open-label, phase II study (TAB).J Clin Oncol2024;42:800-7

[317] Li Z,Chan MT.The role of microRNAs in intrahepatic cholangiocarcinoma.J Cell Mol Med2017;21:177-84 PMCID:PMC5192883

[318] Zheng B,Zhu Y,Xia Q.miRNA and lncRNA as biomarkers in cholangiocarcinoma(CCA).Oncotarget2017;8:100819-30 PMCID:PMC5725067

[319] Jalil AT,Al-Ameer LR.Small but mighty: how microRNAs drive the deadly progression of cholangiocarcinoma.Pathol Res Pract2023;247:154565

[320] Chen L,Yang W.The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma.J Hepatol2009;50:358-69

[321] Oishi N,Roessler S.Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma.Hepatology2012;56:1792-803 PMCID:PMC3458130

[322] Zhang MY,Huang GL.Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis.BMC Cancer2015;15:64 PMCID:PMC4344737

[323] Tiemin P,Qingfu L.Dysregulation of the miR-148a-GLUT1 axis promotes the progression and chemoresistance of human intrahepatic cholangiocarcinoma.Oncogenesis2020;9:19 PMCID:PMC7018977

[324] Chen B,Liu X.miR-22 as a prognostic factor targets glucose transporter protein type 1 in breast cancer.Cancer Lett2015;356:410-7

[325] Zhang T,Li F.miR-143 regulates memory T cell differentiation by reprogramming T cell metabolism.J Immunol2018;201:2165-75

[326] Xu G,Zhu Z.Overexpression of miR-340 inhibits cell proliferation and induces apoptosis of human bladder cancer via targeting Glut-1.BMC Urol2021;21:168 PMCID:PMC8641194

[327] R P Jr,Sekaran S.miRNA associated with glucose transporters in oral squamous cell carcinoma: a systematic review.Cureus2023;15:e46057 PMCID:PMC10605560

[328] Shi Y,Ran F.Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect.Cancer Lett2020;495:53-65

[329] Lu M,Zhou Y.LncRNA HOTAIR suppresses cell apoptosis, autophagy and induces cell proliferation in cholangiocarcinoma by modulating the miR-204-5p/HMGB1 axis.Biomed Pharmacother2020;130:110566

[330] Obaid M,Alluri P.LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation.Sci Rep2021;11:232 PMCID:PMC7794310

[331] Li F,Xue H,Wang K.LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis.Cell Death Dis2020;11:894 PMCID:PMC7581777

[332] Chen J,Li H.Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer.Mol Cancer2019;18:33 PMCID:PMC6397746

[333] Fang R,Fang Z.MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene.J Biol Chem2012;287:23227-35 PMCID:PMC3391126

[334] Liu T,Ye Y.MicroRNA-216b targets HK2 to potentiate autophagy and apoptosis of breast cancer cells via the mTOR signaling pathway.Int J Biol Sci2021;17:2970-83 PMCID:PMC8326127

[335] Jin F,Zhu Y.The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma.Sci Rep2017;7:3089 PMCID:PMC5465066

[336] Muthukumaran N, Velusamy P, Akino Mercy CS, Langford D, Natarajaseenivasan K, Shanmughapriya S. MicroRNAs as regulators of cancer cell energy metabolism.J Pers Med2022;12:1329 PMCID:PMC9410355

[337] Yang Y,Hanse EA.MiR-135 suppresses glycolysis and promotes pancreatic cancer cell adaptation to metabolic stress by targeting phosphofructokinase-1.Nat Commun2019;10:809 PMCID:PMC6379428

[338] Xu Z,Zhang M.miR-122-5p inhibits the proliferation, invasion and growth of bile duct carcinoma cells by targeting ALDOA.Cell Physiol Biochem2018;48:2596-606

[339] Kong L,Zhao L,Li N.Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1 and activation of the ERK/MAPK signaling pathway.Cell Cycle2019;18:1212-28 PMCID:PMC6592249

[340] Zhu H,Jiang X.Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122.J Cancer Res Clin Oncol2016;142:969-80 PMCID:PMC11819340

[341] Cui K,Du Y.Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA.Cancer Cell Int2019;19:202 PMCID:PMC6668142

[342] Chen B,Zeng X.Roles of microRNA on cancer cell metabolism.J Transl Med2012;10:228 PMCID:PMC3563491

[343] Qu Y,Zheng Y.Upregulated miR378a3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT1/ALDOA/PKM2 axis in esophageal carcinoma.Oncol Lett2023;26:421 PMCID:PMC10472027

[344] Fu J,Wu MY.MicroRNA-34 family in cancers: role, mechanism, and therapeutic potential.Cancers2023;15:4723 PMCID:PMC10571940

[345] Chang YC,Chiou J.Nonenzymatic function of aldolase A downregulates miR-145 to promote the Oct4/DUSP4/TRAF4 axis and the acquisition of lung cancer stemness.Cell Death Dis2020;11:195 PMCID:PMC7080828

[346] Peng C,Li O.Leptin stimulates the epithelialmesenchymal transition and proangiogenic capability of cholangiocarcinoma cells through the miR122/PKM2 axis.Int J Oncol2019;55:298-308

[347] Faramin Lashkarian M,Niaraki N.MicroRNA-122 in human cancers: from mechanistic to clinical perspectives.Cancer Cell Int2023;23:29 PMCID:PMC9940444

[348] Li H,Li C.MiR-1286 inhibits lung cancer growth through aerobic glycolysis by targeting PKM2.Arch Med Sci2023;19:151-9 PMCID:PMC9897099

[349] Sun Y,Zhao Q.Down-regulating the expression of miRNA-21 inhibits the glucose metabolism of A549/DDP cells and promotes cell death through the PI3K/AKT/mTOR/HIF-1α pathway.Front Oncol2021;11:653596 PMCID:PMC8144645

[350] Pan C,Wu X.HIF1α/miR-520a-3p/AKT1/mTOR feedback promotes the proliferation and glycolysis of gastric cancer cells.Cancer Manag Res2019;11:10145-56 PMCID:PMC8144645

[351] Guo Z,Ding R,Zhang B.Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues.Sci Rep2014;4:5150 PMCID:PMC5381490

[352] Wu HQ,Lai JM.Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a.PLoS Comput Biol2017;13:e1005618 PMCID:PMC5536358

[353] Bhanot H,Reddy MM.Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming.Oncotarget2017;8:67639-50 PMCID:PMC5620199

[354] Chan B,Sukhatme VP.6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met.Biochem Biophys Res Commun2013;439:247-51

[355] Zheng W,Liu J.Inhibition of 6-phosphogluconate dehydrogenase reverses cisplatin resistance in ovarian and lung cancer.Front Pharmacol2017;8:421 PMCID:PMC5491617

[356] Liao YN,Pan H.Prolactin receptor potentiates chemotherapy through miRNAs-induced G6PD/TKT inhibition in pancreatic cancer.FASEB J2024;38:e23705

[357] Qiu Z,Wang Q.MicroRNA-124 reduces the pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells.Gastroenterology2015;149:1587-98.e11

[358] Yang H,Wu KH,Ju LL.MicroRNA-497 regulates cisplatin chemosensitivity of cervical cancer by targeting transketolase.Am J Cancer Res2016;6:11:2690-99 PMCID:PMC5126283

[359] Ding J,Yuan X.MicroRNA-mediated reprogramming of glucose, fatty acid and amino acid metabolism in cancer.GENOME INSTAB DIS2023;4:47-69

[360] Nikolova E,Milev M.miRNAs and related genetic biomarkers according to the WHO glioma classification: From diagnosis to future therapeutic targets.Noncoding RNA Res2024;9:141-52 PMCID:PMC10686814

[361] Zhang S,Liu J,Xu H.PGC-1 alpha interacts with microRNA-217 to functionally regulate breast cancer cell proliferation.Biomed Pharmacother2017;85:541-8

[362] Qian L,Deng C.Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal Transduct Target Ther2024;9:50 PMCID:PMC10904817

[363] Zhu R,Ma Y.miR-23b-3p suppressing PGC1α promotes proliferation through reprogramming metabolism in osteosarcoma.Cell Death Dis2019;10:381 PMCID:PMC6522531