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2000
Volume 25, Issue 24
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Sodium‒glucose cotransporter 2 (SGLT2) inhibitors have become viable therapeutic options for treating breast cancer. Diabetes is the primary source of these medications. This research examines how SGLT2 blockers can induce apoptosis, decrease the amount of glucose taken up by cancer cells, and modify key signaling pathways, such as the PI3K/AKT/mTOR and MAPK pathways. The effects of four different SGLT2 inhibitors on breast cancer cells were investigated in this study both and testing: dapagliflozin, ipragliflozin, canagliflozin, and empagliflozin. The potential synergistic effects of these inhibitors with conventional chemotherapy medications were also examined. This review explores the complex relationship between SGLT2 inhibitors and breast cancer, examining how drugs interact with this disease at various stages of its development. Additionally, this study highlights how SGLT2 inhibitors may be used in conjunction with precision medicine techniques to treat breast cancer. Although encouraging outcomes have been noted, this review highlights the necessity of additional clinical studies to evaluate the safety and effectiveness of SGLT2 blockers in patients with breast cancer, in addition to ongoing research into the molecular mechanisms underlying the anticancer effects of these drugs.

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2025-04-14
2025-12-14
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References

  1. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.21763 36633525
    [Google Scholar]
  2. Age and Cancer Risk2021https://www.cancer.gov/about-cancer/causes-prevention/risk/age
  3. Breast Cancer Facts & Figures.American Cancer Society2024
    [Google Scholar]
  4. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
    [Google Scholar]
  5. HongR. XuB. Breast cancer: An up‐to‐date review and future perspectives.Cancer Commun.2022421091393610.1002/cac2.12358 36074908
    [Google Scholar]
  6. RejR.K. RoyJ. AlluS.R. Therapies for the treatment of advanced/metastatic estrogen receptor-positive breast cancer: Current situation and future directions.Cancers202416355210.3390/cancers16030552
    [Google Scholar]
  7. ŁukasiewiczS. CzeczelewskiM. FormaA. BajJ. SitarzR. StanisławekA. Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—an updated review.Cancers20211317428710.3390/cancers13174287 34503097
    [Google Scholar]
  8. DugganC. DvaladzeA. RositchA.F. GinsburgO. YipC.H. HortonS. Camacho RodriguezR. EniuA. MutebiM. BourqueJ.M. MasoodS. Unger-SaldañaK. CabanesA. CarlsonR.W. GralowJ.R. AndersonB.O. The breast health global initiative 2018 global summit on improving breast healthcare through resource‐stratified phased implementation: Methods and overview.Cancer2020126S10Suppl. 102339235210.1002/cncr.32891 32348573
    [Google Scholar]
  9. XieF. LiuL. YangH. LiuM. WangS. GuoJ. YuL. ZhouF. WangF. XiangY. YuZ. WangS. The impact of reproductive factors on the risk of breast cancer by ER/PR and HER2: A multicenter case-control study in Northern and Eastern China.Oncologist2022271e1e810.1093/oncolo/oyab018 35305101
    [Google Scholar]
  10. AlblowyA.H. MaanN. IbrahimA.A. Optimal control strategies for SGLT2 inhibitors as a novel anti-tumor agent and their effect on human breast cancer cells with the effect of time delay and hyperglycemia.Comput. Biol. Med.202316610755210.1016/j.compbiomed.2023.107552 37826954
    [Google Scholar]
  11. LegaI.C. LipscombeL.L. Review: Diabetes, obesity, and cancer—pathophysiology and clinical implications.Endocr. Rev.2020411335210.1210/endrev/bnz014 31722374
    [Google Scholar]
  12. KomatsuS. NomiyamaT. NumataT. KawanamiT. HamaguchiY. IwayaC. HorikawaT. Fujimura-TanakaY. HamanoueN. MotonagaR. TanabeM. InoueR. YanaseT. KawanamiD. SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation.Endocr. J.20206719910610.1507/endocrj.EJ19‑0428 31776304
    [Google Scholar]
  13. MiziakP. BaranM. BłaszczakE. Przybyszewska-PodstawkaA. KałafutJ. Smok-KalwatJ. Dmoszyńska-GraniczkaM. KiełbusM. StepulakA. Estrogen receptor signaling in breast cancer.Cancers20231519468910.3390/cancers15194689 37835383
    [Google Scholar]
  14. ChungC.T. LakhaniI. ChouO.H.I. LeeT.T.L. DeeE.C. NgK. WongW.T. LiuT. LeeS. ZhangQ. CheungB.M.Y. TseG. ZhouJ. Sodium‐glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors on new‐onset overall cancer in Type 2 diabetes mellitus: A population‐based study.Cancer Med.20231211122991231510.1002/cam4.5927 37148547
    [Google Scholar]
  15. ZhouJ. ZhuJ. YuS.J. MaH.L. ChenJ. DingX.F. ChenG. LiangY. ZhangQ. Sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces glucose uptake to induce breast cancer cell growth arrest through AMPK/mTOR pathway.Biomed. Pharmacother.202013211082110.1016/j.biopha.2020.110821 33068934
    [Google Scholar]
  16. KennedyS.P. O’NeillM. CunninghamD. MorrisP.G. ToomeyS. Blanco-AparicioC. MartinezS. PastorJ. EustaceA.J. HennessyB.T. Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.Oncogene202039143028304010.1038/s41388‑020‑1202‑y 32042115
    [Google Scholar]
  17. LiuG. ZhuJ. YuM. CaiC. ZhouY. YuM. FuZ. GongY. YangB. LiY. ZhouQ. LinQ. YeH. YeL. ZhaoX. LiZ. ChenR. HanF. TangC. ZengB. Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients.J. Transl. Med.201513114410.1186/s12967‑015‑0500‑6 25947346
    [Google Scholar]
  18. YangC. KoB. HensleyC.T. JiangL. WastiA.T. KimJ. SudderthJ. CalvarusoM.A. LumataL. MitscheM. RutterJ. MerrittM.E. DeBerardinisR.J. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport.Mol. Cell201456341442410.1016/j.molcel.2014.09.025 25458842
    [Google Scholar]
  19. Di ConzaG. TsaiC.H. HoP.C. Fifty shades of α-ketoglutarate on cellular programming.Mol. Cell20197611310.1016/j.molcel.2019.09.002
    [Google Scholar]
  20. JinL. LiD. AlesiG.N. FanJ. KangH.B. LuZ. BoggonT.J. JinP. YiH. WrightE.R. DuongD. SeyfriedN.T. EgnatchikR. DeBerardinisR.J. MaglioccaK.R. HeC. ArellanoM.L. KhouryH.J. ShinD.M. KhuriF.R. KangS. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth.Cancer Cell201527225727010.1016/j.ccell.2014.12.006 25670081
    [Google Scholar]
  21. PapadopoliD. UchenunuO. PaliaR. ChekkalN. HuleaL. TopisirovicI. PollakM. St-PierreJ. Perturbations of cancer cell metabolism by the antidiabetic drug canagliflozin.Neoplasia202123439139910.1016/j.neo.2021.02.003 33784591
    [Google Scholar]
  22. NasiriA.R. RodriguesM.R. LiZ. LeitnerB.P. PerryR.J. SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.Cancer Metab.2019711010.1186/s40170‑019‑0203‑1 31867105
    [Google Scholar]
  23. NavarroC. OrtegaÁ. SantelizR. GarridoB. ChacínM. GalbanN. VeraI. De SanctisJ.B. BermúdezV. Metabolic reprogramming in cancer cells: Emerging molecular mechanisms and novel therapeutic approaches.Pharmaceutics2022146130310.3390/pharmaceutics14061303
    [Google Scholar]
  24. WangY. NasiriA.R. DamskyW.E. PerryC.J. ZhangX.M. Rabin-CourtA. PollakM.N. ShulmanG.I. PerryR.J. Uncoupling hepatic oxidative phosphorylation reduces tumor growth in two murine models of colon cancer.Cell Rep.2018241475510.1016/j.celrep.2018.06.008 29972790
    [Google Scholar]
  25. RiegT. VallonV. Development of SGLT1 and SGLT2 inhibitors.Diabetologia201861102079208610.1007/s00125‑018‑4654‑7
    [Google Scholar]
  26. PerryR.J. ShulmanG.I. Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks.J. Biol. Chem.202029542143791439010.1074/jbc.REV120.008387 32796035
    [Google Scholar]
  27. DuW. MachalzD. YanQ. SorensenE.J. WolberG. BureikM. Importance of asparagine-381 and arginine-487 for substrate recognition in CYP4Z1.Biochem. Pharmacol.202017411385010.1016/j.bcp.2020.113850 32044355
    [Google Scholar]
  28. OkuA. UetaK. NawanoM. ArakawaK. Kano-IshiharaT. MatsumotoM. SaitoA. TsujiharaK. AnaiM. AsanoT. Antidiabetic effect of T-1095, an inhibitor of Na+-glucose cotransporter, in neonatally streptozotocin-treated rats.Eur. J. Pharmacol.20003911-218319210.1016/S0014‑2999(00)00016‑9 10720650
    [Google Scholar]
  29. HsiaD.S. GroveO. CefaluW.T. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus.Curr. Opin. Endocrinol. Diabetes Obes.2017241737910.1097/MED.0000000000000311 27898586
    [Google Scholar]
  30. WashburnW.N. PoucherS.M. Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus.Expert Opin. Investig. Drugs201322446348610.1517/13543784.2013.774372 23452053
    [Google Scholar]
  31. BhattacharyaS. RathoreA. ParwaniD. MallickC. AsatiV. AgarwalS. RajoriyaV. DasR. KashawS.K. An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent.Eur. J. Med. Chem.202020411252310.1016/j.ejmech.2020.112523 32717480
    [Google Scholar]
  32. SaeedM.A. NarendranP. Dapagliflozin for the treatment of type 2 diabetes: A review of the literature.Drug Des. Devel. Ther.201482493250510.2147/DDDT.S50963
    [Google Scholar]
  33. NealB. PerkovicV. MahaffeyK.W. de ZeeuwD. FulcherG. EronduN. ShawW. LawG. DesaiM. MatthewsD.R. Canagliflozin and cardiovascular and renal events in type 2 diabetes.N. Engl. J. Med.2017377764465710.1056/NEJMoa1611925 28605608
    [Google Scholar]
  34. ZinmanB. WannerC. LachinJ.M. FitchettD. BluhmkiE. HantelS. MattheusM. DevinsT. JohansenO.E. WoerleH.J. BroedlU.C. InzucchiS.E. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N. Engl. J. Med.2015373222117212810.1056/NEJMoa1504720 26378978
    [Google Scholar]
  35. VasilakouD. KaragiannisT. AthanasiadouE. MainouM. LiakosA. BekiariE. SarigianniM. MatthewsD.R. TsapasA. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: A systematic review and meta-analysis.Ann. Intern. Med.2013159426227410.7326/0003‑4819‑159‑4‑201308200‑00007 24026259
    [Google Scholar]
  36. JoshiS.S. SinghT. NewbyD.E. SinghJ. Sodium-glucose co-transporter 2 inhibitor therapy: Mechanisms of action in heart failure.Heart2021107131032103810.1136/heartjnl‑2020‑318060
    [Google Scholar]
  37. BaileyR.A. DamarajuC.V. MartinS.C. MeiningerG.E. RupnowM.F.T. BlondeL. Attainment of diabetes-related quality measures with canagliflozin versus sitagliptin.Am. J. Manag. Care2014201Suppl.s16s24 24512193
    [Google Scholar]
  38. KahnS.E. CooperM.E. Del PratoS. Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future.Lancet201438399221068108310.1016/S0140‑6736(13)62154‑6 24315620
    [Google Scholar]
  39. WilcoxG. Insulin and insulin resistance.Clin. Biochem. Rev.20052621939 16278749
    [Google Scholar]
  40. DeFronzoR.A. Banting Lecture. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus.Diabetes200958477379510.2337/db09‑9028 19336687
    [Google Scholar]
  41. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes—2020.Diabetes Care202043Suppl. 1S14S3110.2337/dc20‑S002 31862745
    [Google Scholar]
  42. LeyS.H. HamdyO. MohanV. HuF.B. Prevention and management of type 2 diabetes: dietary components and nutritional strategies.Lancet201438399331999200710.1016/S0140‑6736(14)60613‑9
    [Google Scholar]
  43. SantosL.L. LimaF.J.C. Sousa-RodriguesC.F. BarbosaF.T. Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus.Rev. Assoc. Med. Bras.201763763664110.1590/1806‑9282.63.07.636 28977090
    [Google Scholar]
  44. BasakD. GamezD. DebS. SGLT2 inhibitors as potential anticancer agents.Biomedicines2023117186710.3390/biomedicines11071867 37509506
    [Google Scholar]
  45. SunM. SunJ. SunW. LiX. WangZ. SunL. WangY. Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential.Front. Pharmacol.202415136935210.3389/fphar.2024.1369352 38595915
    [Google Scholar]
  46. AliA. MekhaeilB. BiziotisO.D. TsakiridisE.E. AhmadiE. WuJ. WangS. SinghK. MenjolianG. FarrellT. MesciA. LiuS. BergT. BramsonJ.L. SteinbergG.R. TsakiridisT. The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy.Commun. Biol.20236191910.1038/s42003‑023‑05289‑w 37684337
    [Google Scholar]
  47. KawaguchiT. NakanoD. OkamuraS. ShimoseS. HayakawaM. NiizekiT. KogaH. TorimuraT. Spontaneous regression of hepatocellular carcinoma with reduction in angiogenesis‐related cytokines after treatment with sodium‐glucose cotransporter 2 inhibitor in a cirrhotic patient with diabetes mellitus.Hepatol. Res.201949447948610.1111/hepr.13247 30180287
    [Google Scholar]
  48. KajiK. NishimuraN. SekiK. SatoS. SaikawaS. NakanishiK. FurukawaM. KawarataniH. KitadeM. MoriyaK. NamisakiT. YoshijiH. Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake.Int. J. Cancer201814281712172210.1002/ijc.31193 29205334
    [Google Scholar]
  49. VillaniL.A. SmithB.K. MarcinkoK. FordR.J. BroadfieldL.A. GreenA.E. HoudeV.P. MutiP. TsakiridisT. SteinbergG.R. The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration.Mol. Metab.20165101048105610.1016/j.molmet.2016.08.014 27689018
    [Google Scholar]
  50. NakanoD. KawaguchiT. IwamotoH. HayakawaM. KogaH. TorimuraT. Effects of canagliflozin on growth and metabolic reprograming in hepatocellular carcinoma cells: Multi-omics analysis of metabolomics and absolute quantification proteomics (iMPAQT).PLoS One2020154e023228310.1371/journal.pone.0232283 32343721
    [Google Scholar]
  51. AlKindiF. BoobesY. ShalwaniF. AnsariJ. AlmazroueiR. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) associated diabetic ketoacidosis in oncology patients: A case series and literature review.Cureus2024162e5381610.7759/cureus.53816 38465036
    [Google Scholar]
  52. WuJ.H.Y. FooteC. BlomsterJ. ToyamaT. PerkovicV. SundströmJ. NealB. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: A systematic review and meta-analysis.Lancet Diabetes Endocrinol.20164541141910.1016/S2213‑8587(16)00052‑8 27009625
    [Google Scholar]
  53. KadokuraT. ZhangW. KrauwinkelW. LeeflangS. KeirnsJ. TaniuchiY. NakajoI. SmuldersR. Clinical pharmacokinetics and pharmacodynamics of the novel SGLT2 inhibitor ipragliflozin.Clin. Pharmacokinet.2014531197598810.1007/s40262‑014‑0180‑z 25316572
    [Google Scholar]
  54. Abdul-GhaniM.A. DeFronzoR.A. NortonL. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans.Diabetes201362103324332810.2337/db13‑0604 24065789
    [Google Scholar]
  55. SaishoY. SGLT2 inhibitors: The star in the treatment of type 2 diabetes?Diseases2020821410.3390/diseases8020014 32403420
    [Google Scholar]
  56. BassettR.L. GalloG. LeK.P.N. VolinoL.R. Bexagliflozin: A comprehensive review of a recently approved SGLT2 inhibitor for the treatment of type 2 diabetes mellitus.Med. Chem. Res.2024331354136710.1007/s00044‑024‑03274‑4
    [Google Scholar]
  57. IijimaH. KifujiT. MaruyamaN. InagakiN. Pharmacokinetics, pharmacodynamics, and safety of canagliflozin in japanese patients with type 2 diabetes mellitus.Adv. Ther.201532876878210.1007/s12325‑015‑0234‑0 26280756
    [Google Scholar]
  58. DevineniD. PolidoriD. Clinical pharmacokinetic, pharmacodynamic, and drug-drug interaction profile of canagliflozin, a sodium-glucose co-transporter 2 inhibitor.Clin. Pharmacokinet.201554101027104110.1007/s40262‑015‑0285‑z 26041408
    [Google Scholar]
  59. KasichayanulaS. ChangM. HasegawaM. LiuX. YamahiraN. LaCretaF.P. ImaiY. BoultonD.W. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus.Diabetes Obes. Metab.201113435736510.1111/j.1463‑1326.2011.01359.x 21226818
    [Google Scholar]
  60. WatadaH. ShiramotoM. UedaS. TangW. AsanoM. ThorénF. KimH. YajimaT. BoultonD.W. ArakiE. Pharmacokinetics and pharmacodynamics of dapagliflozin in combination with insulin in Japanese patients with type 1 diabetes.Diabetes Obes. Metab.201921487688210.1111/dom.13593 30499157
    [Google Scholar]
  61. GremplerR. ThomasL. EckhardtM. HimmelsbachF. SauerA. SharpD.E. BakkerR.A. MarkM. KleinT. EickelmannP. Empagliflozin, a novel selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor: Characterisation and comparison with other SGLT‐2 inhibitors.Diabetes Obes. Metab.2012141839010.1111/j.1463‑1326.2011.01517.x 21985634
    [Google Scholar]
  62. HeiseT. SemanL. MachaS. JonesP. MarquartA. PinnettiS. WoerleH.J. DugiK. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus.Diabetes Ther.20134233134510.1007/s13300‑013‑0030‑2 23838841
    [Google Scholar]
  63. MiaoZ. NucciG. AminN. SharmaR. MascittiV. TugnaitM. VazA.D. CallegariE. KalgutkarA.S. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects.Drug Metab. Dispos.201341244545610.1124/dmd.112.049551 23169609
    [Google Scholar]
  64. TerraS.G. FochtK. DaviesM. FriasJ. DerosaG. DarekarA. GolmG. JohnsonJ. SaurD. LauringB. Dagogo-JackS. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.Diabetes Obes. Metab.201719572172810.1111/dom.12888 28116776
    [Google Scholar]
  65. DabourM.S. GeorgeM.Y. DanielM.R. BlaesA.H. ZordokyB.N. The cardioprotective and anticancer effects of SGLT2 inhibitors.JACC Cardiooncol.20246215918210.1016/j.jaccao.2024.01.007 38774006
    [Google Scholar]
  66. TsygankovaO.V. AntipenkoA.G. EvdokimovaN.E. LatyntsevaL.D. BairamovaS.S. BatlukT.I. Difficulties in correction of recurrent hypoglycemia in a patient with a progressive course of malignant metastatic insulinoma.J. Endocrinol. Metab.202010514014310.14740/jem666
    [Google Scholar]
  67. LiangJ. NishiH. BianM.L. HigumaC. SasakiT. ItoH. IsakaK. The ubiquitin-conjugating enzyme E2-EPF is overexpressed in cervical cancer and associates with tumor growth.Oncol. Rep.20122841519152510.3892/or.2012.1949 22895574
    [Google Scholar]
  68. Bocian-JastrzębskaA. Malczewska-HermanA. Kos-KudłaB. Role of leptin and adiponectin in carcinogenesis.Cancers20231517425010.3390/cancers15174250 37686525
    [Google Scholar]
  69. Kadri ColakogluM. BostanciE.B. OzdemirY. DalgicT. AksoyE. OzerI. OzogulY. OterV. Roles of adiponectin and leptin as diagnostic markers in pancreatic cancer.Bratisl. Med. J.2017118739439810.4149/BLL_2017_077 28766348
    [Google Scholar]
  70. YuZ. TangS. MaH. DuanH. ZengY. Association of serum adiponectin with breast cancer.Medicine2019986e1435910.1097/MD.0000000000014359 30732167
    [Google Scholar]
  71. GuiY. PanQ. ChenX. XuS. LuoX. ChenL. The association between obesity related adipokines and risk of breast cancer: A meta-analysis.Oncotarget2017843753897539910.18632/oncotarget.17853 29088874
    [Google Scholar]
  72. MadunićI.V. MadunićJ. BreljakD. KaraicaD. SabolićI. Sodium-glucose cotransporters: New targets of cancer therapy?Arh. Hig. Rada Toksikol.201869427828510.2478/aiht‑2018‑69‑3204 30864374
    [Google Scholar]
  73. CollerH.A. Is cancer a metabolic disease?Am. J. Pathol.2014184141710.1016/j.ajpath.2013.07.035 24139946
    [Google Scholar]
  74. GotoA. YamajiT. SawadaN. MomozawaY. KamataniY. KuboM. ShimazuT. InoueM. NodaM. TsuganeS. IwasakiM. Diabetes and cancer risk: A Mendelian randomization study.Int. J. Cancer2020146371271910.1002/ijc.32310 30927373
    [Google Scholar]
  75. ArgilésJ.M. BusquetsS. StemmlerB. López-SorianoF. J. Cancer cachexia: Understanding the molecular basis.Nat. Rev. Cancer2014141175476210.1038/nrc3829 25291291
    [Google Scholar]
  76. CebiogluM. SchildH. GolubnitschajaO. Diabetes mellitus as a risk factor for cancer: Stress or viral etiology?Infect. Disord. Drug Targets200882768710.2174/187152608784746501 18537703
    [Google Scholar]
  77. LiangL. ChenY. YuY. PanW. CuiY. XuX. PengK. LiuM. RashidK. HouY. LiuT. SLC25A18 has prognostic value in colorectal cancer and represses Warburg effect and cell proliferation via Wnt signaling.Am. J. Cancer Res.202010515481567 32509397
    [Google Scholar]
  78. NakagawaT. LanaspaM.A. MillanI.S. FiniM. RivardC.J. Sanchez-LozadaL.G. Andres-HernandoA. TolanD.R. JohnsonR.J. Fructose contributes to the Warburg effect for cancer growth.Cancer Metab.2020811610.1186/s40170‑020‑00222‑9 32670573
    [Google Scholar]
  79. ShahruzamanS.H. MustafaM.F. RamliS. ManiamS. FakuraziS. ManiamS. The cytotoxic properties of Baeckea frutescens branches extracts in eliminating breast cancer cells.Evid. Based Complement. Alternat. Med.201920191910.1155/2019/9607590 31178918
    [Google Scholar]
  80. JiangX.P. ElliottR.L. HeadJ.F. Exogenous normal mammary epithelial mitochondria suppress glycolytic metabolism and glucose uptake of human breast cancer cells.Breast Cancer Res. Treat.2015153351952910.1007/s10549‑015‑3583‑0 26407856
    [Google Scholar]
  81. NaeimzadehY. TajbakhshA. NematiM. FallahiJ. Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies.Eur. J. Pharmacol.202497817680310.1016/j.ejphar.2024.176803 38950839
    [Google Scholar]
  82. McGillJ.B. SubramanianS. Safety of sodium-glucose co-transporter 2 inhibitors.Am. J. Cardiol.201912410Suppl. 1S45S5210.1016/j.amjcard.2019.10.029 31741440
    [Google Scholar]
  83. BatraS. BamrahP.K. ChoudharyM. Sodium-glucose transporter (SGLT2) inhibition: A potential target for treatment of type-2 Diabetes Mellitus with Natural and Synthetic compounds. Egypt.J. Basic Appl. Sci.2023101698210.1080/2314808X.2022.2145734
    [Google Scholar]
  84. QuagliarielloV. De LaurentiisM. CoccoS. ReaG. BonelliA. CaronnaA. LombariM.C. ConfortiG. BerrettaM. BottiG. MaureaN. NLRP3 as putative marker of ipilimumab-induced cardiotoxicity in the presence of hyperglycemia in estrogen-responsive and triple-negative breast cancer cells.Int. J. Mol. Sci.20202120780210.3390/ijms21207802 33096896
    [Google Scholar]
  85. EliaaS.G. Al-KarmalawyA.A. SalehR.M. ElshalM.F. Empagliflozin and doxorubicin synergistically inhibit the survival of triple-negative breast cancer cells via interfering with the mtor pathway and inhibition of calmodulin: in vitro and molecular docking studies.ACS Pharmacol. Transl. Sci.2020361330133810.1021/acsptsci.0c00144 33344906
    [Google Scholar]
  86. ZhongJ. SunP. XuN. LiaoM. XuC. DingY. CaiJ. ZhangY. XieW. Canagliflozin inhibits p-gp function and early autophagy and improves the sensitivity to the antitumor effect of doxorubicin.Biochem. Pharmacol.202017511385610.1016/j.bcp.2020.113856 32061772
    [Google Scholar]
  87. QuagliarielloV. De LaurentiisM. ReaD. BarbieriA. MontiM.G. CarboneA. PacconeA. AltucciL. ConteM. CanaleM.L. BottiG. MaureaN. The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin.Cardiovasc. Diabetol.202120115010.1186/s12933‑021‑01346‑y 34301253
    [Google Scholar]
  88. JangJ. LeeT.J. SungE.G. SongI.H. KimJ.Y. Dapagliflozin induces apoptosis by downregulating cFILP L and increasing cFILP S instability in Caki 1 cells.Oncol. Lett.202224540110.3892/ol.2022.13521 36276495
    [Google Scholar]
  89. DutkaM. BobińskiR. FrancuzT. GarczorzW. ZimmerK. IlczakT. ĆwiertniaM. HajdugaM.B. SGLT-2 inhibitors in cancer treatment-mechanisms of action and emerging new perspectives.Cancers20221423581110.3390/cancers14235811
    [Google Scholar]
  90. ZakikhaniM. BazileM. HashemiS. JaveshghaniS. AvizonisD. PierreJ.S. PollakM.N. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.PLoS One2012711e4951310.1371/journal.pone.0049513 23185347
    [Google Scholar]
  91. ScafoglioC. HirayamaB.A. KepeV. LiuJ. GhezziC. SatyamurthyN. MoatamedN.A. HuangJ. KoepsellH. BarrioJ.R. WrightE.M. Functional expression of sodium-glucose transporters in cancer.Proc. Natl. Acad. Sci. USA201511230E4111E411910.1073/pnas.1511698112 26170283
    [Google Scholar]
  92. RenD. SunY. ZhangD. LiD. LiuZ. JinX. WuH. SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis.Cancer Lett.202151927728810.1016/j.canlet.2021.07.035 34314754
    [Google Scholar]
  93. ShibusawaR. YamadaE. OkadaS. NakajimaY. BastieC.C. MaeshimaA. KairaK. YamadaM. Dapagliflozin rescues endoplasmic reticulum stress-mediated cell death.Sci. Rep.201991988710.1038/s41598‑019‑46402‑6 31285506
    [Google Scholar]
  94. WangX.Y. YangC.T. ZhengD.D. MoL.Q. LanA.P. YangZ.L. HuF. ChenP.X. LiaoX.X. FengJ.Q. Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress.Mol. Cell. Biochem.20123631-241942610.1007/s11010‑011‑1194‑6 22203419
    [Google Scholar]
  95. SupriyaR. TamB.T. PeiX.M. LaiC.W. ChanL.W. YungB.Y. SiuP.M. Doxorubicin induces inflammatory modulation and metabolic dysregulation in diabetic skeletal muscle.Front. Physiol.2016732310.3389/fphys.2016.00323 27512375
    [Google Scholar]
  96. BastosM.B. BurkhoffD. MalyJ. DaemenJ. den UilC.A. AmelootK. LenzenM. MahfoudF. ZijlstraF. SchreuderJ.J. Van MieghemN.M. Invasive left ventricle pressure-volume analysis: overview and practical clinical implications.Eur. Heart J.202041121286129710.1093/eurheartj/ehz552 31435675
    [Google Scholar]
  97. ChangW.T. LinY.W. HoC.H. ChenZ.C. LiuP.Y. ShihJ.Y. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients.Arch. Toxicol.202195265967110.1007/s00204‑020‑02951‑8 33211168
    [Google Scholar]
  98. ElkhyatS.M. El-MahdyN.A. ElhusseinyM.E. ZidanA-A.A. Impact of dapagliflozin on apoptosis and effector cytotoxic cells using breast cancer cells in mice.Bull. Pharm. Sci.202447
    [Google Scholar]
  99. MaureaN. CanaleM.L. BiscegliaI. IovineM. PalmaG. LucianoA. BruzzeseF. BarbieriM. MaureaC. ZitoF. SabettaR. MontellaM. FrancoR. QuagliarielloV. Dapagliflozin improves radial and longitudinal strain, increases pAMPK and reduces myocardial and renal NF-kB expression in preclinical models of doxorubicin cardiotoxicity through NLRP3 and Myd- 88.Eur. Heart J. Cardiovasc. Imaging202324Suppl. 1jead119.018.10.1093/ehjci/jead119.018
    [Google Scholar]
  100. AkingbesoteN.D. NormanA. ZhuW. HalberstamA.A. ZhangX. FoldiJ. LustbergM.B. PerryR.J. A precision medicine approach to metabolic therapy for breast cancer in mice.Commun. Biol.20225147810.1038/s42003‑022‑03422‑9 35595952
    [Google Scholar]
  101. TilekarK. UpadhyayN. IancuC.V. PokrovskyV. ChoeJ. RamaaC.S. Power of two: Combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochim. Biophys. Acta Rev. Cancer20201874218845710.1016/j.bbcan.2020.188457 33096154
    [Google Scholar]
  102. WareK. SmithT. BrownD.V. HillD. StewartL. The effect of sodium glucose transporter 2 inhibitors on proliferation and growth factor signaling pathways in triple negative breast cancer.FASEB J.201933S110.1096/fasebj.2019.33.1_supplement.647.48
    [Google Scholar]
  103. HsuF.C. LeeH.L. ChenY.J. ShenY.A. TsaiY.C. WuM.H. KuoC.C. LuL.S. YehS.D. HuangW.S. ShenC.N. ChiouJ.F. A few-shot learning approach assists in the prognosis prediction of magnetic resonance-guided focused ultrasound for the local control of bone metastatic lesions.Cancers202214244510.3390/cancers14020445 35053608
    [Google Scholar]
  104. WangX. ZhangJ. LiuX. WeiB. ZhanL. Long noncoding RNAs in endometriosis: Biological functions, expressions, and mechanisms.J. Cell. Physiol.2021236161410.1002/jcp.29847 32506425
    [Google Scholar]
  105. SabaaM. SharawyM.H. El-SherbinyM. SaidE. SalemH.A. IbrahimT.M. Canagliflozin interrupts mTOR-mediated inflammatory signaling and attenuates DMBA-induced mammary cell carcinoma in rats.Biomed. Pharmacother.202215511367510.1016/j.biopha.2022.113675 36115110
    [Google Scholar]
  106. DąbrowskiM. Diabetes, antidiabetic medications and cancer risk in type 2 diabetes: Focus on SGLT-2 inhibitors.Int. J. Mol. Sci.2021224168010.3390/ijms22041680 33562380
    [Google Scholar]
  107. LuisG. GodfroidA. NishiumiS. CiminoJ. BlacherS. MaquoiE. WeryC. CollignonA. LonguespéeR. Montero-RuizL. DassoulI. MaloujahmoumN. PottierC. MazzucchelliG. DepauwE. BellahcèneA. YoshidaM. NoelA. SounniN.E. Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence.Redox Biol.20214310200610.1016/j.redox.2021.102006 34030117
    [Google Scholar]
  108. ChenZ. WangW. Abdul RazakS.R. HanT. AhmadN.H. LiX. Ferroptosis as a potential target for cancer therapy.Cell Death Dis.202314746010.1038/s41419‑023‑05930‑w 37488128
    [Google Scholar]
  109. Samare-NajafM. SamarehA. SavardashtakiA. KhajehyarN. TajbakhshA. VakiliS. MoghadamD. RastegarS. MohsenizadehM. JahromiB.N. VafadarA. ZareiR. Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis.Crit. Rev. Oncol. Hematol.202419410424910.1016/j.critrevonc.2023.104249 38145831
    [Google Scholar]
  110. KarimS. A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells.Oncol. Res.202432581783010.32604/or.2024.048988 38686050
    [Google Scholar]
  111. SmothersA.R. HendersonJ.R. O’ConnellJ.J. StenbeckJ.M. DeanD. HarveyT.G. BoothB.W. Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device.Discov. Oncol.20231413410.1007/s12672‑023‑00647‑w 36991198
    [Google Scholar]
  112. GeJ. ZuoW. ChenY. ShaoZ. YuK. The advance of adjuvant treatment for triple-negative breast cancer.Cancer Biol. Med.202119218720110.20892/j.issn.2095‑3941.2020.0752
    [Google Scholar]
  113. SohailM. SunZ. LiY. GuX. XuH. Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy.Expert Rev. Anticancer Ther.202121121385139810.1080/14737140.2021.1991316 34636282
    [Google Scholar]
  114. UzmaFaridi Fahad Al-Mutairi; Humaira Parveen; Sahar Khateeb, An in vitro and in silico anticancer study of fda approved antidiabetic drugs glimepiride and empagliflozin.Int. J. Life Sci. Pharma Res.202210.22376/ijpbs/lpr.2020.10.2.L52‑57
    [Google Scholar]
  115. AnkerS.D. ButlerJ. Empagliflozin, calcium, and SGLT1/2 receptor affinity: Another piece of the puzzle.ESC Heart Fail.20185454955110.1002/ehf2.12345 30024112
    [Google Scholar]
  116. MustrophJ. WagemannO. LüchtC.M. TrumM. HammerK.P. SagC.M. LebekS. TarnowskiD. ReindersJ. PerbelliniF. TerraccianoC. SchmidC. SchopkaS. HilkerM. ZausigY. PabelS. SossallaS.T. SchwedaF. MaierL.S. WagnerS. Empagliflozin reduces CA/calmodulin‐dependent kinase II activity in isolated ventricular cardiomyocytes.ESC Heart Fail.20185464264810.1002/ehf2.12336 30117720
    [Google Scholar]
  117. NallaL.V. KhairnarA. Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer.Eur. J. Pharmacol.202394317556510.1016/j.ejphar.2023.175565 36739077
    [Google Scholar]
  118. SamaanT.M.A. SamecM. LiskovaA. KubatkaP. BüsselbergD. Paclitaxel’s mechanistic and clinical effects on breast cancer.Biomolecules201991278910.3390/biom9120789
    [Google Scholar]
  119. WuW. WangY. XieJ. FanS. Empagliflozin: A potential anticancer drug.Discov. Oncol.202314112710.1007/s12672‑023‑00719‑x 37436535
    [Google Scholar]
  120. GarczorzW. KosowskaA. FrancuzT. Antidiabetic drugs in breast cancer patients.Cancers202416229910.3390/cancers16020299 38254789
    [Google Scholar]
  121. GunasekaranD. ShiraliA.C. How sweet it is: A perspective on the potential anti-tumor role for SGLT2 inhibitors.Kidney360202349e1322e132410.34067/KID.0000000000000219 37487034
    [Google Scholar]
  122. HuangY.M. ChenW.M. JaoA.T. ChenM. ShiaB.C. WuS.Y. Effects of SGLT2 inhibitors on clinical cancer survival in patients with type 2 diabetes.Diabetes Metab.202450110150010.1016/j.diabet.2023.101500 38036054
    [Google Scholar]
  123. DicembriniI. NreuB. MannucciE. MonamiM. Sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors and cancer: A meta‐analysis of randomized controlled trials.Diabetes Obes. Metab.20192181871187710.1111/dom.13745 30972917
    [Google Scholar]
  124. TsunokakeS. IwabuchiE. MikiY. KanaiA. OnoderaY. SasanoH. IshidaT. SuzukiT. SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.Breast Cancer Res. Treat.2023201349951310.1007/s10549‑023‑07024‑9 37439959
    [Google Scholar]
  125. ChongJ.H. ChangW.T. ChanJ.J. TanT.J.Y. ChanJ.W.K. WongM. WongF.Y. ChuahC.T.H. The cardioprotective potential of sodium-glucose cotransporter 2-inhibitors in breast cancer therapy-related cardiac dysfunction - A systematic review.Curr. Probl. Cardiol.202449310237210.1016/j.cpcardiol.2024.102372 38281354
    [Google Scholar]
  126. LoiblS. GianniL. HER2-positive breast cancer.Lancet2017389100872415242910.1016/S0140‑6736(16)32417‑5 27939064
    [Google Scholar]
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