|
1
|
Bray F, Laversanne M, Sung H, Ferlay J,
Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics
2022: GLOBOCAN estimates of incidence and mortality worldwide for
36 cancers in 185 countries. CA Cancer J Clin. 74:229–263.
2024.PubMed/NCBI
|
|
2
|
Mellman I, Coukos G and Dranoff G: Cancer
immunotherapy comes of age. Nature. 480:480–489. 2011. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Wang DR, Wu XL and Sun YL: Therapeutic
targets and biomarkers of tumor immunotherapy: Response versus
non-response. Signal Transduct Target Ther. 7:3312022. View Article : Google Scholar : PubMed/NCBI
|
|
4
|
Yang L, Ning Q and Tang SS: Recent
advances and next breakthrough in immunotherapy for cancer
treatment. J Immunol Res. 2022:80522122022.PubMed/NCBI
|
|
5
|
Kong X, Zhang J, Chen S, Wang X, Xi Q,
Shen H and Zhang R: Immune checkpoint inhibitors: Breakthroughs in
cancer treatment. Cancer Biol Med. 21:451–472. 2024.PubMed/NCBI
|
|
6
|
Weiss SA and Sznol M: Resistance
mechanisms to checkpoint inhibitors. Curr Opin Immunol. 69:47–55.
2021. View Article : Google Scholar : PubMed/NCBI
|
|
7
|
Dobosz P, Stępień M, Golke A and
Dzieciątkowski T: Challenges of the immunotherapy: Perspectives and
limitations of the immune checkpoint inhibitor treatment. Int J Mol
Sci. 23:28472022. View Article : Google Scholar : PubMed/NCBI
|
|
8
|
Hunter RW, Hughey CC, Lantier L, Sundelin
EI, Peggie M, Zeqiraj E, Sicheri F, Jessen N, Wasserman DH and
Sakamoto K: Metformin reduces liver glucose production by
inhibition of fructose-1-6-bisphosphatase. Nat Med. 24:1395–1406.
2018. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Horakova O, Kroupova P, Bardova K,
Buresova J, Janovska P, Kopecky J and Rossmeisl M: Metformin
acutely lowers blood glucose levels by inhibition of intestinal
glucose transport. Sci Rep. 9:61562019. View Article : Google Scholar : PubMed/NCBI
|
|
10
|
Zhou ZY, Ren LW, Zhan P, Yang HY, Chai DD
and Yu ZW: Metformin exerts glucose-lowering action in high-fat fed
mice via attenuating endotoxemia and enhancing insulin signaling.
Acta Pharmacol Sin. 37:1063–1075. 2016. View Article : Google Scholar : PubMed/NCBI
|
|
11
|
Hua Y, Zheng Y, Yao Y, Jia R, Ge S and
Zhuang A: Metformin and cancer hallmarks: Shedding new lights on
therapeutic repurposing. J Transl Med. 21:4032023. View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Foretz M, Guigas B and Viollet B:
Metformin: Update on mechanisms of action and repurposing
potential. Nat Rev Endocrinol. 19:460–476. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
13
|
O'Connor L, Bailey-Whyte M, Bhattacharya
M, Butera G, Hardell KNL, Seidenberg AB, Castle PE and
Loomans-Kropp HA: Association of metformin use and cancer
incidence: A systematic review and meta-analysis. J Natl Cancer
Inst. 116:518–529. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
14
|
Mu W, Jiang Y, Liang G, Feng Y and Qu F:
Metformin: A promising antidiabetic medication for cancer
treatment. Curr Drug Targets. 24:41–54. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
15
|
Lu Y, Xin D, Guan L, Xu M, Yang Y, Chen Y,
Yang Y, Wang-Gillam A, Wang L, Zong S and Wang F: Metformin
downregulates PD-L1 expression in esophageal squamous cell
catrcinoma by inhibiting IL-6 signaling pathway. Front Oncol.
11:7625232021. View Article : Google Scholar : PubMed/NCBI
|
|
16
|
Turpin R, Liu R, Munne PM, Peura A,
Rannikko JH, Philips G, Boeckx B, Salmelin N, Hurskainen E,
Suleymanova I, et al: Respiratory complex I regulates dendritic
cell maturation in explant model of human tumor immune
microenvironment. J Immunother Cancer. 12:e0080532024. View Article : Google Scholar : PubMed/NCBI
|
|
17
|
Nishida M, Yamashita N, Ogawa T, Koseki K,
Warabi E, Ohue T, Komatsu M, Matsushita H, Kakimi K, Kawakami E, et
al: Mitochondrial reactive oxygen species trigger
metformin-dependent antitumor immunity via activation of
Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes. J
Immunother Cancer. 9:e0029542021. View Article : Google Scholar : PubMed/NCBI
|
|
18
|
Hanahan D, Michielin O and Pittet MJ:
Convergent inducers and effectors of T cell paralysis in the tumour
microenvironment. Nat Rev Cancer. 25:41–58. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
19
|
Yao K, Zheng H and Li T: Association
between metformin use and the risk, prognosis of gynecologic
cancer. Front Oncol. 12:9423802022. View Article : Google Scholar : PubMed/NCBI
|
|
20
|
Brancher S, Støer NC, Weiderpass E,
Damhuis RAM, Johannesen TB, Botteri E and Strand TE: Metformin use
and lung cancer survival: A population-based study in Norway. Br J
Cancer. 124:1018–1025. 2021. View Article : Google Scholar : PubMed/NCBI
|
|
21
|
Almeida-Nunes DL, Silvestre R,
Dinis-Oliveira RJ and Ricardo S: Enhancing immunotherapy in ovarian
cancer: The emerging role of metformin and statins. Int J Mol Sci.
25:3232023. View Article : Google Scholar : PubMed/NCBI
|
|
22
|
Zhu L, Yang K, Ren Z, Yin D and Zhou Y:
Metformin as anticancer agent and adjuvant in cancer combination
therapy: Current progress and future prospect. Transl Oncol.
44:1019452024. View Article : Google Scholar : PubMed/NCBI
|
|
23
|
Munoz LE, Huang L, Bommireddy R, Sharma R,
Monterroza L, Guin RN, Samaranayake SG, Pack CD, Ramachandiran S,
Reddy SJC, et al: Metformin reduces PD-L1 on tumor cells and
enhances the anti-tumor immune response generated by vaccine
immunotherapy. J Immunother Cancer. 9:e0026142021. View Article : Google Scholar : PubMed/NCBI
|
|
24
|
Cha JH, Yang WH, Xia W, Wei Y, Chan LC,
Lim SO, Li CW, Kim T, Chang SS, Lee HH, et al: Metformin promotes
antitumor immunity via endoplasmic-reticulum-associated degradation
of PD-L1. Mol Cell. 71:606–620.e7. 2018. View Article : Google Scholar : PubMed/NCBI
|
|
25
|
Eikawa S, Nishida M, Mizukami S, Yamazaki
C, Nakayama E and Udono H: Immune-mediated antitumor effect by type
2 diabetes drug, metformin. Proc Natl Acad Sci USA. 112:1809–1814.
2015. View Article : Google Scholar : PubMed/NCBI
|
|
26
|
Wabitsch S, McCallen JD, Kamenyeva O, Ruf
B, McVey JC, Kabat J, Walz JS, Rotman Y, Bauer KC, Craig AJ, et al:
Metformin treatment rescues CD8+ T-cell response to immune
checkpoint inhibitor therapy in mice with NAFLD. J Hepatol.
77:748–760. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
27
|
Chiang CH, Chen YJ, Chiang CH, Chen CY,
Chang YC, Wang SS, See XY, Horng CS, Peng CY, Hsia YP, et al:
Effect of metformin on outcomes of patients treated with immune
checkpoint inhibitors: A retrospective cohort study. Cancer Immunol
Immunother. 72:1951–1956. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
28
|
Afzal MZ, Mercado RR and Shirai K:
Efficacy of metformin in combination with immune checkpoint
inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant
melanoma. J Immunother Cancer. 6:642018. View Article : Google Scholar : PubMed/NCBI
|
|
29
|
Page MJ, Bossuyt PM, Boutron I, Boutron I,
Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan
SE, et al: The PRISMA 2020 statement: An updated guideline for
reporting systematic reviews. Int J Surg. 88:1059062021. View Article : Google Scholar : PubMed/NCBI
|
|
30
|
Higgins JPT, Thomas J, Chandler J,
Cumpston M, Li T, Page MJ and Welch VA: Cochrane Handbook for
Systematic Reviews of Interventions. 2nd edition. John Wiley &
Sons; Chichester: 2019, View Article : Google Scholar
|
|
31
|
Wells GA, Shea B, O'Connell D, Peterson J,
Welch V, Losos M and Tugwell P: The newcastle-ottawa scale (NOS)
for assessing the quality of nonrandomised studies in
meta-analyses. Ottawa Hospital Research Institute; 2014
|
|
32
|
Begg CB and Mazumdar M: Operating
characteristics of a rank correlation test for publication bias.
Biometrics. 50:1088–1101. 1994. View
Article : Google Scholar : PubMed/NCBI
|
|
33
|
Afzal MZ, Dragnev K, Sarwar T and Shirai
K: Clinical outcomes in non-small-cell lung cancer patients
receiving concurrent metformin and immune checkpoint inhibitors.
Lung Cancer Manag. 8:LMT112019. View Article : Google Scholar : PubMed/NCBI
|
|
34
|
Wang DY, McQuade JL, Rai RR, Park JJ, Zhao
S, Ye F, Beckermann KE, Rubinstein SM, Johnpulle R, Long GV, et al:
The impact of nonsteroidal anti-inflammatory drugs, beta blockers,
and metformin on the efficacy of anti-PD-1 therapy in advanced
melanoma. Oncologist. 25:e602–e605. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
35
|
Gaucher L, Adda L, Séjourné A, Joachim C,
Guillaume C, Poulet C, Liabeuf S, Gras-Champel V, Masmoudi K,
Houessinon A, et al: Associations between dysbiosis-inducing drugs,
overall survival and tumor response in patients treated with immune
checkpoint inhibitors. Ther Adv Med Oncol.
13:175883592110005912021. View Article : Google Scholar : PubMed/NCBI
|
|
36
|
Cortellini A, Di Maio M, Nigro O, Leonetti
A, Cortinovis DL, Aerts JG, Guaitoli G, Barbieri F, Giusti R,
Ferrara MG, et al: Differential influence of antibiotic therapy and
other medications on oncological outcomes of patients with
non-small cell lung cancer treated with first-line pembrolizumab
versus cytotoxic chemotherapy. J Immunother Cancer. 9:e0024212021.
View Article : Google Scholar : PubMed/NCBI
|
|
37
|
Yang J, Kim SH, Jung EH, Kim SA, Suh KJ,
Lee JY, Kim JW, Kim JW, Lee JO, Kim YJ, et al: The effect of
metformin or dipeptidyl peptidase 4 inhibitors on clinical outcomes
in metastatic non-small cell lung cancer treated with immune
checkpoint inhibitors. Thorac Cancer. 14:52–60. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
38
|
Fiala O, Buti S, Takeshita H, Okada Y,
Massari F, Palacios GA, Dionese M, Scagliarini S, Büttner T,
Fornarini G, et al: Use of concomitant proton pump inhibitors,
statins or metformin in patients treated with pembrolizumab for
metastatic urothelial carcinoma: Data from the ARON-2 retrospective
study. Cancer Immunol Immunother. 72:3665–3682. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
39
|
Wang J, Lin J and Guo H, Wu W, Yang J, Mao
J, Fan W, Qiao H, Wang Y, Yan X and Guo H: Prognostic impact of
metformin in solid cancer patients receiving immune checkpoint
inhibitors: Novel evidences from a multicenter retrospective study.
Front Pharmacol. 15:14194982024. View Article : Google Scholar : PubMed/NCBI
|
|
40
|
Wen J, Yi Z, Chen Y, Huang J, Mao X, Zhang
L, Zeng Y, Cheng Q, Ye W, Liu Z, et al: Efficacy of metformin
therapy in patients with cancer: A meta-analysis of 22 randomised
controlled trials. BMC Med. 20:4022022. View Article : Google Scholar : PubMed/NCBI
|
|
41
|
Shen J, Ye X, Hou H and Wang Y: Clinical
evidence for the prognostic impact of metformin in cancer patients
treated with immune checkpoint inhibitors. Int Immunopharmacol.
134:1122432024. View Article : Google Scholar : PubMed/NCBI
|
|
42
|
Xue J, Li L, Li N, Li F, Qin X, Li T and
Liu M: Metformin suppresses cancer cell growth in endometrial
carcinoma by inhibiting PD-L1. Eur J Pharmacol. 859:1725412019.
View Article : Google Scholar : PubMed/NCBI
|
|
43
|
Wang Z, Lu C, Zhang K, Lin C, Wu F, Tang
X, Wu D, Dou Y, Han R, Wang Y, et al: Metformin combining PD-1
inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer
through AXIN-1-dependent inhibition of STING ubiquitination. Front
Mol Biosci. 9:7802002022. View Article : Google Scholar : PubMed/NCBI
|
|
44
|
Jiang H, Suo H, Gao L, Liu Y, Chen B, Lu
S, Jin F and Cao Y: Metformin plays an antitumor role by
downregulating inhibitory cells and immune checkpoint molecules
while activating protective immune responses in breast cancer. Int
Immunopharmacol. 118:1100382023. View Article : Google Scholar : PubMed/NCBI
|
|
45
|
Kim K, Yang WH, Jung YS and Cha JH: A new
aspect of an old friend: The beneficial effect of metformin on
anti-tumor immunity. BMB Rep. 53:512–520. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
46
|
Panaampon J, Zhou Y and Saengboonmee C:
Metformin as a booster of cancer immunotherapy. Int
Immunopharmacol. 121:1105282023. View Article : Google Scholar : PubMed/NCBI
|
|
47
|
Tan X, Li Y, Hou Z, Zhang M, Li L and Wei
J: Combination therapy with PD-1 inhibition plus rapamycin and
metformin enhances anti-tumor efficacy in triple negative breast
cancer. Exp Cell Res. 429:1136472023. View Article : Google Scholar : PubMed/NCBI
|
|
48
|
Park JH, Jung KH, Jia D, Yang S, Attri KS,
Ahn S, Murthy D, Samanta T, Dutta D, Ghidey M, et al: Biguanides
antithetically regulate tumor properties by the dose-dependent
mitochondrial reprogramming-driven c-Src pathway. Cell Rep Med.
6:1019412025. View Article : Google Scholar : PubMed/NCBI
|
|
49
|
Garstka MA, Kedzierski L and Maj T:
Diabetes can impact cellular immunity in solid tumors. Trends
Immunol. 46:295–309. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
50
|
Salmon H, Remark R, Gnjatic S and Merad M:
Host tissue determinants of tumour immunity. Nat Rev Cancer.
19:215–227. 2019.PubMed/NCBI
|
|
51
|
Giraldo NA, Becht E, Vano Y, Petitprez F,
Lacroix L, Validire P, Sanchez-Salas R, Ingels A, Oudard S, Moatti
A, et al: Tumor-infiltrating and peripheral blood T-cell
immunophenotypes predict early relapse in localized clear cell
renal cell carcinoma. Clin Cancer Res. 23:4416–4428. 2017.
View Article : Google Scholar : PubMed/NCBI
|
|
52
|
Ganss R: Tumour vessel remodelling: New
opportunities in cancer treatment. Vasc Biol. 2:R35–R43. 2020.
View Article : Google Scholar : PubMed/NCBI
|
|
53
|
Reck M, Rodríguez-Abreu D, Robinson AG,
Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe
S, et al: Pembrolizumab versus chemotherapy for PD-L1-positive
non-small-cell lung cancer. N Engl J Med. 375:1823–1833. 2016.
View Article : Google Scholar : PubMed/NCBI
|
|
54
|
Burtness B, Harrington KJ, Greil R,
Soulières D, Tahara M, de Castro G Jr, Psyrri A, Basté N, Neupane
P, Bratland Å, et al: Pembrolizumab alone or with chemotherapy
versus cetuximab with chemotherapy for recurrent or metastatic
squamous cell carcinoma of the head and neck (KEYNOTE-048): A
randomised, open-label, phase 3 study. Lancet. 394:1915–1928. 2019.
View Article : Google Scholar : PubMed/NCBI
|
|
55
|
Larkin J, Chiarion-Sileni V, Cowey CL,
Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R,
Smylie M, et al: Combined nivolumab and ipilimumab or monotherapy
in untreated melanoma. N Engl J Med. 373:23–34. 2015. View Article : Google Scholar : PubMed/NCBI
|
|
56
|
Bouchi R, Kondo T, Ohta Y, Goto A, Tanaka
D, Satoh H, Yabe D, Nishimura R, Harada N, Kamiya H, et al: A
consensus statement from the Japan Diabetes Society: A proposed
algorithm for pharmacotherapy in people with type 2 diabetes. J
Diabetes Investig. 14:151–164. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
57
|
Lin C, Xia M, Dai Y, Huang Q, Sun Z, Zhang
G, Luo R, Peng Q, Li J, Wang X, et al: Cross-ancestry analyses of
Chinese and European populations reveal insights into the genetic
architecture and disease implication of metabolites. Cell Genom.
5:1008102025. View Article : Google Scholar : PubMed/NCBI
|
