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2000
Volume 25, Issue 26
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Introduction

The persistent drug resistance observed in lung cancer necessitates innovative strategies to improve therapeutic outcomes. This review investigates the potential of combining metformin (Met) and cisplatin (Cis) to overcome drug resistance and enhance treatment efficacy. Cis's limitations, including drug resistance and adverse effects, coupled with Met’s established safety profile, form the backdrop for this exploration.

Methods

Systematic literature searches across major databases identified relevant studies exploring the synergistic effects of Met and Cis in the context of drug-resistant lung cancer. Data extraction encompassed diverse facets, including treatment protocols, cellular responses, and mechanistic insights. The synthesis of these findings sheds light on the potential of this combination therapy to combat drug resistance.

Results

Numerous and studies have demonstrated the ability of the Met + Cis combination to sensitize drug-resistant lung cancer cells. The co-treatment consistently showed enhanced inhibition of cell proliferation, elevated apoptosis rates, and attenuated migration and invasion capabilities compared to monotherapies. Mechanistically, Met’s modulatory effect on key pathways, such as AMPK-mTOR and ROS-mediated signaling, appears to underlie its ability to counter drug resistance.

Conclusion

The Met + Cis combination holds promise as an innovative strategy to counter drug resistance in lung cancer. By harnessing the synergistic effects of these agents, combination therapy offers a novel approach to enhance treatment efficacy and mitigate the challenges posed by drug-resistant lung cancer. Although further clinical validation is required, the Met + Cis synergy represents a promising avenue in the pursuit of improved lung cancer therapy outcomes.

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References

  1. NazariN. A. SarajarB. O. AzarshinS. Z. JouniF. J. RazzaghiZ. ZafariJ. Overcoming cisplatin’s challenges: A promising future in cancer care; A comprehensive review.IJMTFM2023134
     [Google Scholar]
  2. SharmaP. MehtaM. DhanjalD.S. KaurS. GuptaG. SinghH. ThangaveluL. RajeshkumarS. TambuwalaM. BakshiH.A. ChellappanD.K. DuaK. SatijaS. Emerging trends in the novel drug delivery approaches for the treatment of lung cancer.Chem. Biol. Interact.201930910872010.1016/j.cbi.2019.06.033 31226287
     [Google Scholar]
  3. Rezagholi LalaniA. EbrahimbabaieF. SojoudiM. PouyaniN.R. Salari SharifabadM. FakhariF. RezaeiS. Multi-target hybrid drugs: A promising approach for treating alzheimer’s, neurological diseases, diabetes, and cancer.J. Chem. Health Risks2023
     [Google Scholar]
  4. DeoS.V.S. SharmaJ. KumarS. GLOBOCAN 2020 report on global cancer burden: Challenges and opportunities for surgical oncologists.Ann. Surg. Oncol.202229116497650010.1245/s10434‑022‑12151‑6 35838905
     [Google Scholar]
  5. MeloskyB. KambartelK. HäntschelM. BennettsM. NickensD.J. BrinkmannJ. KayserA. MoranM. CappuzzoF. Worldwide prevalence of epidermal growth factor receptor mutations in non-small cell lung cancer: A meta-analysis.Mol. Diagn. Ther.202226171810.1007/s40291‑021‑00563‑1 34813053
     [Google Scholar]
  6. LalaniA.R. Rastegar-PouyaniN. AskariA. TavajohiS. AkbariS. JafarzadehE. Food additives, benefits, and side effects: A review article.J. Chem. Health Risks2024141
     [Google Scholar]
  7. VinodS.K. HauE. Radiotherapy treatment for lung cancer: Current status and future directions.Respirology202025S2Suppl. 2617110.1111/resp.13870 32516852
     [Google Scholar]
  8. DaweD.E. HarlosC.H. JuergensR.A. Immuno-oncology-the new paradigm of lung cancer treatment.Curr. Oncol.20202712Suppl. 2788610.3747/co.27.5183 32368177
     [Google Scholar]
  9. HuangC.Y. JuD.T. ChangC.F. Muralidhar ReddyP. VelmuruganB.K. A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer.Biomedicine (Taipei)2017742310.1051/bmdcn/2017070423 29130448
     [Google Scholar]
  10. SzejniukW.M. RoblesA.I. McCullochT. FalkmerU.G.I. RøeO.D. Epigenetic predictive biomarkers for response or outcome to platinum-based chemotherapy in non-small cell lung cancer, current state-of-art.Pharmacogenomics J.201919151410.1038/s41397‑018‑0029‑1 30190521
     [Google Scholar]
  11. ArdizzoniA. BoniL. TiseoM. FossellaF.V. SchillerJ.H. PaesmansM. RadosavljevicD. PaccagnellaA. ZatloukalP. MazzantiP. BissetD. RosellR. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: An individual patient data meta-analysis.J. Natl. Cancer Inst.2007991184785710.1093/jnci/djk196 17551145
     [Google Scholar]
  12. ZhongH. SunS. ChenJ. WangZ. ZhaoY. ZhangG. ChenG. ZhouM. ZhouJ. DuY. WuL. XuZ. MeiX. ZhangW. HeJ. CuiJ. ZhangZ. LuoH. LiuW. SunM. WuJ. ShenY. ZhangS. YangN. WangM. LuJ. LiK. YaoW. SunQ. YueH. WangL. YeS. LiB. ZhuangX. PanY. ZhangM. ShuY. HeZ. PanL. LingY. LiuS. ZhangQ. JiaoS. HanB. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): A multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial.Lancet Respir. Med.202412535536510.1016/S2213‑2600(23)00431‑9 38309287
     [Google Scholar]
  13. JafarzadehE. MontazeriV. AliebrahimiS. SezavarA.H. GhahremaniM.H. OstadS.N. Combined regimens of cisplatin and metformin in cancer therapy: A systematic review and meta-analysis.Life Sci.202230412068010.1016/j.lfs.2022.120680 35662589
     [Google Scholar]
  14. LinS.R. ChangC.H. HsuC.F. TsaiM.J. ChengH. LeongM.K. SungP.J. ChenJ.C. WengC.F. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence.Br. J. Pharmacol.202017761409142310.1111/bph.14816 31368509
     [Google Scholar]
  15. HuangZ. XiaoZ. YuL. LiuJ. YangY. OuyangW. Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets.Crit. Rev. Oncol. Hematol.202419610428410.1016/j.critrevonc.2024.104284 38311012
     [Google Scholar]
  16. EstebsariF. Rahimi KhalifehkandiZ. LatifiM. FarhadinasabA. VasliP. MostafaieD. Protection motivation theory and prevention of breast cancer: A systematic review.Clin. Breast Cancer2023234e239e24610.1016/j.clbc.2023.02.013 37045635
     [Google Scholar]
  17. ZafariJ. Rastegar-PouyaniN. Javani JouniF. NajjarN. AzarshinS.Z. JafarzadehE. AbdolmalekiP. Hoseini ShiraziF. Static magnetic field reduces cisplatin resistance via increasing apoptosis pathways and genotoxicity in cancer cell lines.Sci. Rep.2024141579210.1038/s41598‑024‑56605‑1 38461218
     [Google Scholar]
  18. ZafariJ. ZadehmodarresS. Javani JouniF. Bagheri-HosseinabadiZ. NajjarN. AsnaashariM. Investigation into the effect of photodynamic therapy and cisplatin on the cervical cancer cell line (A2780).J. Lasers Med. Sci.202011Suppl. 1S85S9110.34172/jlms.2020.S14 33995975
     [Google Scholar]
  19. BoulikasT. VougioukaM. Recent clinical trials using cisplatin, carboplatin and their combination chemotherapy drugs (Review).Oncol. Rep.200411355959510.3892/or.11.3.559 14767508
     [Google Scholar]
  20. TchounwouP.B. DasariS. NoubissiF.K. RayP. KumarS. Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy.J. Exp. Pharmacol.20211330332810.2147/JEP.S267383 33776489
     [Google Scholar]
  21. AbadiA.J. MirzaeiS. MahabadyM.K. HashemiF. ZabolianA. HashemiF. RaeeP. AghamiriS. AshrafizadehM. ArefA.R. HamblinM.R. HushmandiK. ZarrabiA. SethiG. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects.Phytother. Res.202236118921310.1002/ptr.7305 34697839
     [Google Scholar]
  22. JalaliA. ZafariJ. JouniF.J. AbdolmalekiP. ShiraziF.H. KhodayarM.J. Combination of static magnetic field and cisplatin in order to reduce drug resistance in cancer cell lines.Int. J. Radiat. Biol.20199581194120110.1080/09553002.2019.1589012 30822212
     [Google Scholar]
  23. HabibiP. OstadS.N. MonazzamM.R. ForoushaniA.R. Ghazi-KhansariM. AliebrahimiS. MontazeriV. GolbabaeiF. Thermal stress and TiO2 nanoparticle–induced oxidative DNA damage and apoptosis in mouse hippocampus.Environ. Sci. Pollut. Res. Int.20222960901289013910.1007/s11356‑022‑21796‑5 35864393
     [Google Scholar]
  24. GavrilasL.I. CruceriuD. MocanA. LoghinF. MiereD. BalacescuO. Plant-derived bioactive compounds in colorectal cancer: Insights from combined regimens with conventional chemotherapy to overcome drug-resistance.Biomedicines2022108194810.3390/biomedicines10081948 36009495
     [Google Scholar]
  25. JouniF.J. ZafariJ. AbbasifardM. JafarisaniM. SadeghiH. Bagheri-HosseinabadiZ. Erratum to: Synergistic effects on taurine and cisplatin on lung cancer cells (A549).Cytol. Genet.202357438438510.3103/S0095452723040047
     [Google Scholar]
  26. ZafariJ. Javani JouniF. AbdolmalekiP. KhodayarM. JalaliA. Toxicity of cisplatin under the influence of static magnetic field in susceptible and drug-resistant cells.Modares Journal of Biotechnology201894621626
     [Google Scholar]
  27. LaMoiaT.E. ShulmanG.I. Cellular and molecular mechanisms of metformin action.Endocr. Rev.2021421779610.1210/endrev/bnaa023 32897388
     [Google Scholar]
  28. JalaliF. FakhariF. SepehrA. ZafariJ. SarajarB.O. SarihiP. JafarzadehE. Synergistic anticancer effects of doxorubicin and metformin combination therapy: A systematic review.Transl. Oncol.20244510194610.1016/j.tranon.2024.101946 38636389
     [Google Scholar]
  29. LvZ. GuoY. Metformin and its benefits for various diseases.Front. Endocrinol. (Lausanne)20201119110.3389/fendo.2020.00191 32425881
     [Google Scholar]
  30. GuptaJ. JalilA.T. Abd AlzahraaZ.H. AminovZ. AlsaikhanF. Ramírez-CoronelA.A. RamaiahP. NajafiM. The metformin immunoregulatory actions in tumor suppression and normal tissues protection.Curr. Med. Chem.202431335370539610.2174/0929867331666230703143907 37403391
     [Google Scholar]
  31. PetrieJ.R. Metformin beyond type 2 diabetes: Emerging and potential new indications.Diabetes Obes. Metab.202426S3Suppl. 3314110.1111/dom.15756 38965738
     [Google Scholar]
  32. ChenY.H. WuJ.X. YangS.F. ChenM.L. ChenT.H. HsiaoY.H. Metformin potentiates the anticancer effect of everolimus on cervical cancer in vitro and in vivo.Cancers (Basel)20211318461210.3390/cancers13184612 34572837
     [Google Scholar]
  33. KhodamoradiE. RahmaniN. RashidiK. NajafiM. ShahsavariS. MohammadiM. Exploring the potential of metformin in mitigating radiation-induced gastrointestinal and hematopoietic system injury in rats after whole-body X-ray radiation: An experimental study.Curr. Radiopharm.202417220020810.2174/0118744710261673231115062547 38231059
     [Google Scholar]
  34. MoralesD.R. MorrisA.D. Metformin in cancer treatment and prevention.Annu. Rev. Med.2015661172910.1146/annurev‑med‑062613‑093128 25386929
     [Google Scholar]
  35. LiberatiA. AltmanD.G. TetzlaffJ. MulrowC. GøtzscheP.C. IoannidisJ.P. ClarkeM. DevereauxP.J. KleijnenJ. MoherD. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.Ann. Intern. Med.20091514W10.7326/0003‑4819‑151‑4‑200908180‑0013619622512
     [Google Scholar]
  36. PageM.J. McKenzieJ.E. BossuytP.M. BoutronI. HoffmannT.C. MulrowC.D. ShamseerL. TetzlaffJ.M. AklE.A. BrennanS.E. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.BMJ2021372
     [Google Scholar]
  37. GrechV. EldawlatlyA.A. STROBE, CONSORT, PRISMA, MOOSE, STARD, SPIRIT, and other guidelines – Overview and application.Saudi J. Anaesth.202418113714110.4103/sja.sja_545_23 38313708
     [Google Scholar]
  38. ChouT.C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.Pharmacol. Rev.200658362168110.1124/pr.58.3.10 16968952
     [Google Scholar]
  39. Salari SharifM. MohseniH.S. KhanaviM. GhadamiS. JafarzadehE. TavajohiS. AliebrahimiS. OstadS.N. Exploring the synergistic effect of sildenafil and green tea polyphenols on breast cancer stem cell-like cells and their parental cells: A potential novel therapeutic approach.Anticancer. Agents Med. Chem.202424430431510.2174/0118715206276925231107060329 37957912
     [Google Scholar]
  40. LinC.C. YehH.H. HuangW.L. YanJ.J. LaiW.W. SuW.P. ChenH.H.W. SuW.C. Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.Am. J. Respir. Cell Mol. Biol.201349224125010.1165/rcmb.2012‑0244OC 23526220
     [Google Scholar]
  41. LiH. YangD. XuZ. YangL. LinJ. CaiJ. YangL. Metformin sensitizes Cisplatin-induced apoptosis through regulating nucleotide excision repair pathway in cisplatin-resistant human lung cancer cells.Lett. Drug Des. Discov.202219121086109510.2174/1570180819666220330121135
     [Google Scholar]
  42. WangY. LinB. WuJ. ZhangH. WuB. Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen-activated protein kinase.Oncol. Lett.2014831269127410.3892/ol.2014.2270 25120704
     [Google Scholar]
  43. WangJ. GaoQ. WangD. WangZ. HuC. Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria-mediated pathway.Oncol. Lett.20151031343134910.3892/ol.2015.3450 26622674
     [Google Scholar]
  44. DongX-L. YangE. SunB-N. LiuY-Q. ZhouJ. Antineoplastic activity of metformin on the A549 human lung carcinoma cell line in vitro.Int. J. Clin. Exp. Med.20171071071110717
     [Google Scholar]
  45. TeixeiraS.F. GuimarãesI.S. MadeiraK.P. DaltoéR.D. SilvaI.V. RangelL.B.A. Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells.J. Bras. Pneumol.201339664464910.1590/S1806‑37132013000600002 24473757
     [Google Scholar]
  46. MorelliA. TortelliT.Jr PavanI. SilvaF. GranatoD. PerucaG. PaulettiB. DominguesR. BezerraR. De MouraL. Paes LemeA. ChammasR. SimabucoF. Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.Int. J. Oncol.20215862810.3892/ijo.2021.5208 33846781
     [Google Scholar]
  47. XiaoZ. GaertnerS. Morresi-HaufA. GenzelR. DuellT. UllrichA. KnyazevP.G. Metformin triggers autophagy to attenuate drug-induced apoptosis in NSCLC cells, with minor effects on tumors of diabetic patients.Neoplasia201719538539510.1016/j.neo.2017.02.011 28391030
     [Google Scholar]
  48. ChenG. ChenY.Q. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice.J. Cancer Res. Ther.201511232433010.4103/0973‑1482.151444 26148594
     [Google Scholar]
  49. HuangS. HeT. YangS. ShengH. TangX. BaoF. WangY. LinX. YuW. ChengF. LvW. HuJ. Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2.Transl. Lung Cancer Res.2020962337235510.21037/tlcr‑20‑1072 33489797
     [Google Scholar]
  50. RiazM.A. SakA. ErolY.B. GronebergM. ThomaleJ. StuschkeM. Metformin enhances the radiosensitizing effect of cisplatin in non-small cell lung cancer cell lines with different cisplatin sensitivities.Sci. Rep.201991128210.1038/s41598‑018‑38004‑5 30718758
     [Google Scholar]
  51. AshinumaH. TakiguchiY. KitazonoS. Kitazono-SaitohM. KitamuraA. ChibaT. TadaY. KurosuK. SakaidaE. SekineI. TanabeN. IwamaA. YokosukaO. TatsumiK. Antiproliferative action of metformin in human lung cancer cell lines.Oncol. Rep.2012281814 22576795
     [Google Scholar]
  52. SayedR. SaadA.S. El WakeelL. ElkholyE. BadaryO. Metformin addition to chemotherapy in stage IV non-small cell lung cancer: An open label randomized controlled study.Asian Pac. J. Cancer Prev.201516156621662610.7314/APJCP.2015.16.15.6621 26434885
     [Google Scholar]
  53. VernieriC. SignorelliD. GalliG. GanzinelliM. MoroM. FabbriA. TamboriniE. MarabeseM. CaiolaE. BrogginiM. HollanderL. GallucciR. VandoniG. GavazziC. TriulziT. ColomboM.P. RizzoA.M. CorsettoP.A. PruneriG. de BraudF. SozziG. TorriV. GarassinoM.C. Exploiting fasting-mimicking diet and metformin to improve the efficacy of platinum-pemetrexed chemotherapy in advanced LKB1-inactivated lung adenocarcinoma: The FAME trial.Clin. Lung Cancer2019203e413e41710.1016/j.cllc.2018.12.011 30617039
     [Google Scholar]
  54. AlamM.S. MalikG. TanwarP. NaagarM. SinghT. SinghO. MaityM.K. A review on small-cell lung cancer: Epidemiology, pathophysiology, risk factors, diagnosis, clinical management and treatment modalities.Int J Curr Sci Res Rev.20236112915110.47191/ijcsrr/V6‑i1‑16
     [Google Scholar]
  55. Chaitanya ThandraK. BarsoukA. SaginalaK. Sukumar AluruJ. BarsoukA. Epidemiology of lung cancer.Contemp. Oncol. (Pozn.)2021251455210.5114/wo.2021.103829 33911981
     [Google Scholar]
  56. Sánchez de Cos EscuínJ. New immunotherapy and lung cancer.Arch. Bronconeumol.2017531268268710.1016/j.arbr.2017.10.014 28823733
     [Google Scholar]
  57. MontazeriV. GhahremaniM.H. MontazeriH. HasanzadM. SafaviD.M. AyatiM. ChehraziM. Arefi MoghaddamB. OstadS.N. A preliminary study of NER and MMR pathways involved in chemotherapy response in bladder transitional cell carcinoma: impact on progression-free survival.Iran. J. Pharm. Res.2020191355365 32922493
     [Google Scholar]
  58. Farnoudian-HabibiA. AliebrahimiS. SehatiF. NabavizadehF. AsadiH. MontazeriV. van NostrumC.F. Rad-MalekshahiM. Nasser OstadS. Development a novel nano-platform for Thrombolysis acceleration by Thrombin sensitive polymer-peptide hybrid nancapsules.Int. J. Pharm.202466312456110.1016/j.ijpharm.2024.124561 39111356
     [Google Scholar]
  59. LiuJ. ChengH. HanL. QiangZ. ZhangX. GaoW. ZhaoK. SongY. Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles.Drug Des. Devel. Ther.2018123199320910.2147/DDDT.S172199 30288024
     [Google Scholar]
  60. WangY. ZhangH. HaoJ. LiB. LiM. XiuwenW. Lung cancer combination therapy: Co-delivery of paclitaxel and doxorubicin by nanostructured lipid carriers for synergistic effect.Drug Deliv.20162341398140310.3109/10717544.2015.1055619 26079530
     [Google Scholar]
  61. MokhtariR.B. HomayouniT.S. BaluchN. MorgatskayaE. KumarS. DasB. YegerH. Combination therapy in combating cancer.Oncotarget2017823380223804310.18632/oncotarget.16723 28410237
     [Google Scholar]
  62. MehdizadehM. MehdizadehZ. JafarzadehE. ChoudhuryA.R. HaghiZ. MatinA. BagheriA. OmidiA. Skin cancer prevention by nutraceuticals. Nutraceuticals in Cancer Prevention, Management, and Treatment.Apple Academic Press2024191213
     [Google Scholar]
  63. JouniF.J. ZafariJ. AbbasifardM. JafarisaniM. Bagheri-HosseinabadiZ. Synergistic effects of taurine and cisplatin on lung cancer cells (A549).Cytol. Genet.202357219720610.3103/S0095452723020044
     [Google Scholar]
  64. KipB. AydinO. Overcome of cisplatin resistance in ovarian cancer by combination of low-intensity ultrasound and Cisplatin.Curr. Drug Deliv.20232091380139010.2174/1567201819666220627100857 35761504
     [Google Scholar]
  65. Javani JouniF. AbdollahiV. ZadehmodarresS. AbbasiniaH. AsnaashariM. ZafariJ. Combination of cisplatin treatment and photodynamic therapy attenuates cisplatin-induced cell toxicity in A2780 and A2780-CP cervical cancer cell lines.Lasers Med. Sci.20223721175118010.1007/s10103‑021‑03369‑z 34255220
     [Google Scholar]
  66. VancuraA. BuP. BhagwatM. ZengJ. VancurovaI. Metformin as an anticancer agent.Trends Pharmacol. Sci.2018391086787810.1016/j.tips.2018.07.006
     [Google Scholar]
  67. BaileyC.J. Metformin: Therapeutic profile in the treatment of type 2 diabetes.Diabetes Obes. Metab.202426S3Suppl. 331910.1111/dom.15663 38784991
     [Google Scholar]
  68. RabahH.M. MohamedD.A. MariahR.A. Abd El-KhalikS.R. KhattabH.A. AbuoHashishN.A. AbdelsattarA.M. RaslanM.A. FarghalE.E. EltokhyA.K. Novel insights into the synergistic effects of selenium nanoparticles and metformin treatment of letrozole - induced polycystic ovarian syndrome: Targeting PI3K/Akt signalling pathway, redox status and mitochondrial dysfunction in ovarian tissue.Redox Rep.2023281216056910.1080/13510002.2022.2160569 36661246
     [Google Scholar]
  69. YenH. ChangY.T. YeeF.J. HuangY.C. Metformin therapy for acne in patients with polycystic ovary syndrome: A systematic review and meta-analysis.Am. J. Clin. Dermatol.2021221112310.1007/s40257‑020‑00565‑5
     [Google Scholar]
  70. LiuY. HeC. HuangX. Metformin partially reverses the carboplatin-resistance in NSCLC by inhibiting glucose metabolism.Oncotarget2017843752067521610.18632/oncotarget.20663 29088858
     [Google Scholar]
  71. RamnathN. DillingT.J. HarrisL.J. KimA.W. MichaudG.C. BalekianA.A. DiekemperR. DetterbeckF.C. ArenbergD.A. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest20131435)(Suppl.e314Se340S10.1378/chest.12‑2360 23649445
     [Google Scholar]
  72. SpiroS.G. PorterJ.C. Lung cancer--where are we today? Current advances in staging and nonsurgical treatment.Am. J. Respir. Crit. Care Med.200216691166119610.1164/rccm.200202‑070SO 12403687
     [Google Scholar]
  73. GholamiM. KlashamiZ.N. EbrahimiP. MahboobipourA.A. FaridA.S. VahidiA. ZoughiM. AsadiM. AmoliM.M. Metformin and long non-coding RNAs in breast cancer.J. Transl. Med.202321115510.1186/s12967‑023‑03909‑x 36849958
     [Google Scholar]
  74. XieW. WangL. ShengH. QiuJ. ZhangD. ZhangL. YangF. TangD. ZhangK. Metformin induces growth inhibition and cell cycle arrest by upregulating microRNA34a in renal cancer cells.Med. Sci. Monit.201723293710.12659/MSM.898710 28045889
     [Google Scholar]
  75. FangZ. XuX. ZhouZ. XuZ. LiuZ. Effect of metformin on apoptosis, cell cycle arrest migration and invasion of A498 cells.Mol. Med. Rep.2014962251225610.3892/mmr.2014.2097 24691570
     [Google Scholar]
  76. ChenZ. WeiH. ZhaoX. XinX. PengL. NingY. WangY. LanY. ZhangQ. Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP‐2 and MMP‐9 via H19/miR‐29b‐3p and AKT/mTOR/autophagy signaling pathways.J. Cell. Physiol.201923411199641997610.1002/jcp.28594 30989649
     [Google Scholar]
  77. UedaS. ShirabeK. MoritaK. UmedaK. KayashimaH. UchiyamaH. SoejimaY. TaketomiA. MaeharaY. Evaluation of ERCC1 expression for cisplatin sensitivity in human hepatocellular carcinoma.Ann. Surg. Oncol.20111841204121110.1245/s10434‑010‑1414‑4 21076943
     [Google Scholar]
  78. Erdemir SayanS. SreekumarR. BhomeR. MirnezamiA. YagciT. SayanA.E. ERCC1 abundance is an indicator of DNA repair-apoptosis decision upon DNA damage.Cell Death Discov.20241014710.1038/s41420‑024‑01817‑7 38272916
     [Google Scholar]
  79. LiQ. ChenS. WangX. CaiJ. HuangH. TangS. HeD. Cisplatin-based combination therapy for enhanced cancer treatment.Curr. Drug Deliv.2024257473491 38591210
     [Google Scholar]
  80. TangZ. TangN. JiangS. BaiY. GuanC. ZhangW. FanS. HuangY. LinH. YingY. The chemosensitizing role of metformin in anti-cancer therapy.Anticancer. Agents Med. Chem.202121894996210.2174/1871520620666200918102642 32951587
     [Google Scholar]
  81. WangX. ZhangH. ChenX. Drug resistance and combating drug resistance in cancer.Cancer Drug Resist.20192214116010.20517/cdr.2019.10 34322663
     [Google Scholar]
  82. EslamiM. MemarsadeghiO. DavarpanahA. ArtiA. NayerniaK. BehnamB. Overcoming chemotherapy resistance in metastatic cancer: A comprehensive review.Biomedicines202412118310.3390/biomedicines12010183 38255288
     [Google Scholar]
  83. YangT. YuS. LiuL. SunY. LanY. MaX. ZhuR. LiL. HouY. LiuY. Dual polymeric prodrug co-assembled nanoparticles with precise ratiometric co-delivery of cisplatin and metformin for lung cancer chemoimmunotherapy.Biomater. Sci.20208205698571410.1039/D0BM01191F 32930254
     [Google Scholar]
  84. MoroM. CaiolaE. GanzinelliM. ZulatoE. RulliE. MarabeseM. CentonzeG. BusicoA. PastorinoU. de BraudF.G. VernieriC. SimboloM. BriaE. ScarpaA. IndraccoloS. BrogginiM. SozziG. GarassinoM.C. Metformin enhances cisplatin-induced apoptosis and prevents resistance to cisplatin in co-mutated KRAS/LKB1 NSCLC.J. Thorac. Oncol.201813111692170410.1016/j.jtho.2018.07.102 30149143
     [Google Scholar]
  85. GreenA.S. ChapuisN. LacombeC. MayeuxP. BouscaryD. TamburiniJ. LKB1/AMPK/mTOR signaling pathway in hematological malignancies: From metabolism to cancer cell biology.Cell Cycle201110132115212010.4161/cc.10.13.16244 21572254
     [Google Scholar]
  86. GengY. WangZ. XuX. SunX. DongX. LuoY. SunX. Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: A systematic review.Transl. Res.2024263739210.1016/j.trsl.2023.08.001 37567440
     [Google Scholar]
  87. RhoS.B. ByunH.J. KimB.R. LeeC.H. Knockdown of LKB1 sensitizes endometrial cancer cells via AMPK activation.Biomol. Ther. (Seoul)202129665065710.4062/biomolther.2021.131 34607979
     [Google Scholar]
  88. WangZ. LiuP. ChenQ. DengS. LiuX. SituH. ZhongS. HannS. LinY. Targeting AMPK signaling pathway to overcome drug resistance for cancer therapy.Curr. Drug Targets201617885386410.2174/1389450116666150316223655 25777274
     [Google Scholar]
  89. LiuB. ZhangJ. ZhangJ. JiX. WangR. GongA. MiaoD. Metformin prevents mandibular bone loss in a mouse model of accelerated aging by correcting dysregulated AMPK-mTOR signaling and osteoclast differentiation.J. Orthop. Translat.20244612914210.1016/j.jot.2024.03.001 38867742
     [Google Scholar]
  90. ZamanianM.Y. GolmohammadiM. YumashevA. HjaziA. ToamaM.A. AbdRabouM.A. GehlotA. AlwailyE.R. ShirsalimiN. YadavP.K. MoriasiG. Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways.Cell Biochem. Funct.2024424e407110.1002/cbf.4071 38863255
     [Google Scholar]
  91. HanB. CuiH. KangL. ZhangX. JinZ. LuL. FanZ. Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway.Tumour Biol.20153686295630410.1007/s13277‑015‑3315‑4 25854169
     [Google Scholar]
  92. LiC. XueY. XiY.R. XieK. Progress in the application and mechanism of metformin in treating non-small cell lung cancer.Oncol. Lett.20171352873288010.3892/ol.2017.5862 28529553
     [Google Scholar]
  93. AbdulghanyZ.S. Metformin enhances the sensitivity of Glioblastoma cancer cells to Cisplatin through DNA damage assessment.Middle East J. Cancer202415298107
     [Google Scholar]
  94. ZhuL. YangK. RenZ. YinD. ZhouY. Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect.Transl. Oncol.20244410194510.1016/j.tranon.2024.101945 38555742
     [Google Scholar]
  95. ZhengY. ZhuJ. ZhangH. LiuY. SunH. Metformin inhibits ovarian cancer growth and migration in vitro and in vivo by enhancing cisplatin cytotoxicity.Am. J. Transl. Res.2018101030863098 30416652
     [Google Scholar]
  96. XiongY. ZhaoY. MiaoL. LinC.M. HuangL. Co-delivery of polymeric metformin and cisplatin by self-assembled coremembrane nanoparticles to treat non-small cell lung cancer.J. Control. Release2016244Pt A637310.1016/j.jconrel.2016.11.00527840166
     [Google Scholar]
  97. TullyE. BhartiS. WooJ. BhujwallaZ. GabrielsonE. Biguanide drugs enhance cytotoxic effects of cisplatin by depleting aspartate and NAD+ in sensitive cancer cells.Cancer Biol. Ther.20212210-1257958610.1080/15384047.2021.1982599 34720054
     [Google Scholar]
  98. TortelliT.C.Jr TamuraR.E. de Souza JunqueiraM. da Silva MororóJ. BustosS.O. NatalinoR.J.M. RussellS. DésaubryL. StraussB.E. ChammasR. Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells.Aging (Albany NY)20211318219142194010.18632/aging.203528 34528900
     [Google Scholar]
  99. JangS.K. HongS.E. LeeD.H. KimJ.Y. KimJ.Y. HongJ. ParkI.C. JinH.O. Inhibition of AKT enhances the sensitivity of NSCLC cells to metformin.Anticancer Res.20214173481348710.21873/anticanres.15135 34230143
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266317788241121100259
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Combating Drug Resistance in Lung Cancer: Exploring the Synergistic Potential of Metformin and Cisplatin in a Novel Combination Therapy; A Systematic Review
Curr. Top. Med. Chem. 25, 3000 (2025); https://doi.org/10.2174/0115680266317788241121100259
/content/journals/ctmc/10.2174/0115680266317788241121100259
/content/journals/ctmc/10.2174/0115680266317788241121100259
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  • Article Type:     Review Article
Keyword(s): combination therapy; drug resistance; Lung Cancer; survival pathways; synergistic approach

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