Metformin and Other Biguanides in Oncology: Advancing the Research Agenda
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Abstract
Retrospective studies that may be impractical to confirm prospectively suggest that diabetics treated with metformin have a substantially reduced cancer burden compared with other diabetics. It is unclear if this reflects a chemopreventive effect, an effect on transformed cells, or both. It also remains to be established if these data have relevance to people without diabetes. Laboratory models, however, provide independent impressive evidence for the activity of metformin and other biguanides in both cancer treatment and chemoprevention. Investigations of mechanisms of action of biguanides have revealed considerable complexity and have identified important gaps in knowledge that should be addressed to ensure the optimal design of clinical trials of these agents. Such trials may define important new indications for biguanides in the prevention and/or treatment of many common cancers. Cancer Prev Res; 3(9); 1060–5. ©2010 AACR.
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Our results indicate that PTEN-negative tumors seem resistant to the anticancer effect of metformin.
“However, our results indicate that PTEN-negative tumors seem resistant to the anticancer effect of metformin, which may be related to another anticancer mechanism of metformin involving adenosine monophosphate-activated protein kinase (AMPK) [3,18].”
From Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14). (2026) · cites this paper as [18]
In “Gaps in Knowledge” (page unavailable), the paper says constitutive PI3K activation would be expected to confer resistance to metformin’s insulin-lowering effects, but not necessarily to its direct actions. “Metformin and Neoplastic Disease: Early Clues” describes an AMPK-dependent anticancer mechanism. The paper does not report that PTEN-negative tumors resist metformin’s anticancer effects overall; the citing authors describe that as their own result. (LLM, conf=0.84)
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BackgroundSelf-citationMartinez‐Outschoorn, U., Goldberg, A. F., Zhao, L., Ko, Y., Flomenberg, N., Wang, C., Pavlides, S., Pestell, R. G., Howell, A., Sotgia, F., et al. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.12.10.17780 · Cited by 175 · see citing works
Metformin and cancer: from the old medicine cabinet to pharmacological pitfalls and prospects
Riedmaier, A. E., Fisel, P., Nies, A. T., Schaeffeler, E., & Schwab, M. G. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.11.005 · Cited by 161 · see citing works
Garrett, C. R., Hassabo, H. M., Bhadkamkar, N. A., Wen, S., Baladandayuthapani, V., Kee, B. K., Eng, C., & Hassan, M. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.71 · Cited by 151 · see citing works
“Thus, in cancer cells metformin inhibited insulin-stimulated mTOR activation and proliferation in an AMPK-dependent manner (Engelman and Cantley, 2010; Pollak, 2010).”
BackgroundMetformin and cancer: An existing drug for cancer prevention and therapy (Review)
Zi, F., Zi, H., Li, Y., He, J., Shi, Q., & Cai, Z. (2017) · Oncology Letters · doi:10.3892/ol.2017.7412 · Cited by 152 · see citing works
“Pollak (81) demonstrated that, while metformin reduced the insulin level, no effect on the IGF-I/IGF-II level was observed (47,77,81).”
Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis
Zhang, H., Gao, C., Fang, L., Zhao, H.-C., & Yao, S. (2012) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2012.719926 · Cited by 147 · see citing works
“Early laboratory studies of biguanides explored antimicrobial activity, and biguanide derivatives are now widely used in applications ranging from swimming pool decontamination to contact lens sterilization, and are under study for AIDS treatment [17].”
BackgroundBosco, J. L. F., Antonsen, S., Sørensen, H. T., Pedersen, L. H., & Lash, T. L. (2011) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-10-0817 · Cited by 148 · see citing works
“Metformin indirectly reduces the level of circulating insulin in diabetic patients andmay reduce the rate of cell proliferation in epithelial cells; therefore, it may also reduce the risk of breast cancer (9).”
BackgroundResultInfluentialLKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective
Ciccarese, F., Zulato, E., & Indraccolo, S. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8730816 · Cited by 147 · see citing works
“Metformin is one of the most widely used type 2 diabetes drug worldwide, and epidemiological studies revealed that diabetic patients taking metformin show a statistically significant reduced tumor incidence [69].”
BackgroundJung, J., Park, S., Lee, S., Seo, M., Trosko, J. E., & Kang, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028068 · Cited by 145 · see citing works
“shown to lower the risk of some diabetes-related tumors, including breast cancer [2–15].”
Vitale-Cross, L. A., Molinolo, A., Martı́n, D., Younis, R. H., Maruyama, T., Patel, V., Chen, W., Schneider, A., & Gutkind, J. S. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0502 · Cited by 143 · see citing works
“In this regard, emerging studies indicate that metformin may lower the risk of cancer and/or improve cancer prognosis in part by inhibiting the mTORC1 pathway (16).”
Mohammed, A., Janakiram, N. B., Brewer, M., Ritchie, R. L., Marya, A., Lightfoot, S., Steele, V. E., & Rao, C. V. (2013) · Translational Oncology · doi:10.1593/tlo.13556 · Cited by 142 · see citing works
Metformin for aging and cancer prevention
Anisimov, V. N. (2010) · Aging · doi:10.18632/aging.100230 · Cited by 140 · see citing works
“It is important to stress that hyperinsulinemia is also an important factor in development of cancer [39,40-45].”
BackgroundSex and gender influences on pharmacological response: an overview
Franconi, F., & Campesi, I. (2014) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2014.922866 · Cited by 132 · see citing works
“Furthermore, the anticancer activity of metformin could be associated with a decrease in insulin resistance and the inhibition of IGF-1R/IR, Akt, ERK and mTOR phosphorylation [243].”
BackgroundNair, V., Sreevalsan, S., Basha, R., Abdelrahim, M., Abudayyeh, A., Rodrigues Hoffman, A., & Safe, S. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.592576 · Cited by 129 · see citing works
“The potential clinical applications for metformin in cancer chemotherapy also stems from reports on the anticancer activities of this drug in cancer cells in culture and in in vivo models (1-4,13-28).”
BackgroundKoehler, J. A., Kain, T., & Drucker, D. J. (2011) · Endocrinology · doi:10.1210/en.2011-1201 · Cited by 129 · see citing works
“and/or transformation remain incompletely understood (2).”
Phenformin as an Anticancer Agent: Challenges and Prospects
Rubiño, M. E. G., Carrillo, E., Ruiz-Alcalá, G., Domínguez‐Martín, A., Marchal, J. A., & Boulaiz, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133316 · Cited by 121 · see citing works
“In lung tumors, it has been proven that phenformin has a greater bioavailability and is able to induce more potent stress energy than metformin [61].”
BackgroundEffects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle
Hadad, S. M., Hardie, D. G., Appleyard, V., & Thompson, A. M. (2013) · Clinical & Translational Oncology · doi:10.1007/s12094-013-1144-8 · Cited by 113 · see citing works
“One proposal is that the effects of metformin in cancer are due to its hypoglycemic actions in insulin-resistant individuals, thus reducing the plasma concentration of insulin and/or insulin-like growth factor-1 (IGF1), which can act as growth factors for tumor cells [18].”
BackgroundThe effect of metformin and thiazolidinedione use on lung cancer in diabetics
Mazzone, P. J., Rai, H., Beukemann, M., Meng, X., Jain, A., & Sasidhar, M. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-410 · Cited by 112 · see citing works
“that the biguanide metformin and the class of thiazolidinediones (TZDs) may have cancer suppressing effects [12,13].”
BackgroundMetabolic interplays between the tumour and the host shape the tumour macroenvironment
Altea‐Manzano, P., Decker-Farrell, A. R., Janowitz, T., & Erez, A. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00786-4 · Cited by 127 · see citing works
Metformin Induces Apoptosis through AMPK-Dependent Inhibition of UPR Signaling in ALL Lymphoblasts
Leclerc, G. M., Leclerc, G. J., Kuznetsoff, J. N., DeSalvo, J., & Barredo, J. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074420 · Cited by 106 · see citing works
“Its anti-cancer effect is supported by epidemiological studies that show a decrease in cancer incidence in metformin-treated patients [14].”
BackgroundCuzick, J. M. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30536-3 · Cited by 106 · see citing works
Role of AMPK in UVB-induced DNA damage repair and growth control
Wu, C. L., Qiang, L., Han, W., Ming, M., Viollet, B., & He, Y. Y. (2013) · Oncogene · doi:10.1038/onc.2012.279 · Cited by 105 · see citing works
“Over the past few years, however, impressive evidence from several studies indicates that metformin exhibits cancer prevention effects in vitro and in animal models (28, 29).”
BackgroundMultiple Molecular Pathways in Melanomagenesis: Characterization of Therapeutic Targets
Palmieri, G., Ombra, M. N., Colombino, M., Casula, M., Sini, M. C., Manca, A., Paliogiannis, P., Ascierto, P. A., & Cossu, A. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00183 · Cited by 104 · see citing works
Nair, V., Pathi, S. S., Jutooru, I., Sreevalsan, S., Basha, R. M., Abdelrahim, M., Samudio, I. J., & Safe, S. H. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt231 · Cited by 100 · see citing works
Vázquez‐Martín, A., Vellón, L., Quirós, P. M., Cufí, S., de Galarreta, E. R., Oliveras‐Ferraros, C., Martín, Á. G., Martı́n-Castillo, B., López-Otı́n, C., & Menéndez, J. A. (2012) · Cell Cycle · doi:10.4161/cc.11.5.19450 · Cited by 98 · see citing works
The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology
Pollak, M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0998 · Cited by 97 · see citing works
Self-citationTargeting LKB1 in Cancer – Exposing and Exploiting Vulnerabilities
Momcilovic, M., & Shackelford, D. B. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.261 · Cited by 97 · see citing works
“Several retrospective studies revealed a strong correlation between reduced cancer risk and mortality in diabetic patients taking metformin (Evans et al, 2005; Bowker et al, 2006; Pollak, 2010; Currie et al, 2012), agreeing with early studies showing that biguanides suppressed naturally arising tumours in both transge…”
ResultHadad, S. M., Coates, P. J., Jordan, L. B., Dowling, R. J. O., Chang, M. C., Done, S. J., Purdie, C. A., Goodwin, P. J., Stambolic, V., Moulder-Thompson, S. L., et al. (2015) · Breast Cancer Research and Treatment · doi:10.1007/s10549-015-3307-5 · Cited by 94 · see citing works
“A systemic effect, reducing the circulating insulin that may act as a growth-promoting agent [13] and/or insulin-like growth factor-1 (IGF1) [14] was supported by the mean serum insulin remaining stable in patients receiving metformin but rising in control patients [15].”
BackgroundJanda, M., Robledo, K. P., Gebski, V., Armes, J. E., Alizart, M., Cummings, M. C., Chen, C., Leung, Y. C., Sykes, P. H., McNally, O., et al. (2021) · Gynecologic Oncology · doi:10.1016/j.ygyno.2021.01.029 · Cited by 94 · see citing works
Association Between Metformin Use and Risk of Prostate Cancer and Its Grade
Margel, D., Urbach, D. R., Lipscombe, L. L., Bell, C. M., Kulkarni, G. S., Austin, P. C., & Fleshner, N. E. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt170 · Cited by 91 · see citing works
Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer
Lambe, M. P., Wigertz, A., Garmo, H., Walldius, G., Jungner, I., & Hammar, N. (2011) · Cancer Causes & Control · doi:10.1007/s10552-011-9794-8 · Cited by 91 · see citing works
“There are reports of associations between use of antidiabetics and cancer risk and mortality, with metformin associated with a decreased risk and sulfonylurea and insulin with an increased risk [40– 42].”
BackgroundO’Brien, A. J., Villani, L. A., Broadfield, L. A., Houde, V. P., Galić, S., Blandino, G., Kemp, B. E., Tsakiridis, T. K., Muti, P. C., & Steinberg, G. R. (2015) · Biochemical Journal · doi:10.1042/bj20150122 · Cited by 89 · see citing works
Relevance of the OCT1 transporter to the antineoplastic effect of biguanides
Segal, E., Yasmeen, A., Beauchamp, M.-C., Rosenblatt, J., Pollak, M., & Gotlieb, W. H. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.09.134 · Cited by 90 · see citing works
“It has already been recognized that some of these biomarkers may be related to host characteristics such as degree of hyperinsulinemia, while others may be related to mechanism of cellular action, such as functionality of the LKB1-AMPK signaling system [28].”
BackgroundSelf-citationTargeting the insulin growth factor receptor 1
Arnaldez, F. I., & Helman, L. J. (2012) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2012.01.004 · Cited by 88 · see citing works
“Initially used as an antidiabetic drug that reduces both glucose and insulin plasma concentrations, the role of this agent in cancer therapy is an exciting area of current research that is beyond the limits of this review and has been described elsewhere.(118) Patients treated with metformin seem to have a lower incid…”
BackgroundBost, F., Sahra, I. B., MARCHAND‐BRUSTEL, Y. L., & Tanti, J. (2011) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32834d8155 · Cited by 88 · see citing works
“Several reports established a direct action of metformin on cancer cells (for review see [7,15]).”
BackgroundThe Use of Metformin and the Incidence of Lung Cancer in Patients With Type 2 Diabetes
Smiechowski, B., Azoulay, L., Yin, H., Pollak, M., & Suissa, S. (2012) · Diabetes Care · doi:10.2337/dc12-0740 · Cited by 86 · see citing works
Self-citationPritchard, K. I., Shepherd, L. E., Chapman, J. W., Norris, B. D., Cantin, J., Goss, P. E., Dent, S. F., Walde, D., Vandenberg, T. A., Findlay, B., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.7006 · Cited by 85 · see citing works
Self-citationMetformin in obesity, cancer and aging: addressing controversies
Berstein, L. M. (2012) · Aging · doi:10.18632/aging.100455 · Cited by 85 · see citing works
“Of special interest is the question of whether metformin is the most appropriate biguanide for oncology [36, 53, 95] and beyond.”
BackgroundMenéndez, J. A., Cufí, S., Oliveras‐Ferraros, C., Martı́n-Castillo, B., Joven, J., Vellón, L., & Vázquez‐Martín, A. (2011) · Aging · doi:10.18632/aging.100407 · Cited by 84 · see citing works
“This suggests that the anti-cancer effects of metformin largely depend on (or are restricted to) its preventive effects [118].”
BackgroundCicero, A. F. G., Tartagni, E., & Ertek, S. (2012) · Archives of Medical Science · doi:10.5114/aoms.2012.31622 · Cited by 82 · see citing works
“Metformin is one of the most frequently used drugs worldwide, with an estimated 40 million prescriptions in the USA alone in the year 2008, its safety allowing a large area of use [122].”
BackgroundLeptin and Adiponectin: Emerging Therapeutic Targets in Breast Cancer
Surmacz, E. (2013) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-013-9302-8 · Cited by 80 · see citing works
Malek, M. A. Y. A., Jagannathan, S., Malek, E., Sayed, D. M., Elgammal, S. A., El-Azeem, H. G. A., Thabet, N. M., & Driscoll, J. J. (2014) · Oncotarget · doi:10.18632/oncotarget.3075 · Cited by 81 · see citing works
Inhibition of Melanogenesis by the Antidiabetic Metformin
Lehraiki, A., Abbe, P., Cerezo, M., Rouaud, F., Regazzetti, C., Chignon‐Sicard, B., Passeron, T., Bertolotto, C., Ballotti, R., & Rocchi, S. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.202 · Cited by 81 · see citing works
“Recent studies indicate that metformin can potentially be used as an efficient anticancer drug in various tumors (Ben Sahra et al., 2010; Pollak, 2010).”
BackgroundMetformin prevents cell tumorigenesis through autophagy-related cell death
Santi, M. D., Baldelli, G., Diotallevi, A., Galluzzi, L., Schiavano, G. F., & Brandi, G. (2019) · Scientific Reports · doi:10.1038/s41598-018-37247-6 · Cited by 76 · see citing works
lncRNA NBR2 modulates cancer cell sensitivity to phenformin through GLUT1
Liu, X., & Gan, B. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1249545 · Cited by 76 · see citing works
“been increasing interest to re-examine phenformin as a potential agent in cancer prevention and treatment.(1-3,14)”
BackgroundMetformin impairs the growth of liver kinase B1-intact cervical cancer cells
Xiao, X., He, Q., Lu, C., Werle, K. D., Zhao, R.-X., Chen, J., Davis, B. C., Cui, R., Liang, J., & Xu, Z.-X. (2012) · Gynecologic Oncology · doi:10.1016/j.ygyno.2012.06.032 · Cited by 75 · see citing works
“Metformin is a biguanide derivative that has been widely used for treating diabetes mellitus [48].”
BackgroundRedaniel, M. T., Jeffreys, M., May, M., Ben‐Shlomo, Y., & Martin, R. M. (2012) · Cancer Causes & Control · doi:10.1007/s10552-012-0057-0 · Cited by 75 · see citing works
“We were not able to control for stage, tumor grade, and morphology, but our results are consistent with existing literature [13, 19, 23].”
BackgroundResultInhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions
Gutkind, J. S., Molinolo, A., Wu, X., Wang, Z., Nachmanson, D., Harismendy, O., Alexandrov, L. B., Wuertz, B. R. K., Ondrey, F. G., Laronde, D. M., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.147096 · Cited by 73 · see citing works
A spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer
Khan, A., & Frigo, D. E. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2016.272 · Cited by 72 · see citing works
Metformin as an antitumor agent in cancer prevention and treatment
Li, D. (2011) · Journal of Diabetes · doi:10.1111/j.1753-0407.2011.00119.x · Cited by 68 · see citing works
“However, there are several key questions that need to be addressed before clinical trials can be optimally designed.(54) For example, how do we identify high-risk individuals who are most likely to benefit from metformin treatment? What are the optimal doses that should be used? What biomarkers could predict responses…”
BackgroundVrachnis, N., Iavazzo, C. R., Iliodromiti, Z., Sifakis, S., Alexandrou, A. P., Siristatidis, C. S., Grigoriadis, C., Botsis, D. S., & Creatsas, G. C. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-015-3858-z · Cited by 68 · see citing works
“cancer risk, while metformin seems to lower the risk [1].”
BackgroundTherapeutic aspects of AMPK in breast cancer: Progress, challenges, and future directions
Ponnusamy, L., Natarajan, S. R., Thangaraj, K., & Manoharan, R. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188379 · Cited by 67 · see citing works
Hawkes, A. L., Quinn, M. A., Gebski, V., Armes, J. E., Brennan, D. J., Janda, M., & Obermair, A. (2014) · Contemporary Clinical Trials · doi:10.1016/j.cct.2014.06.014 · Cited by 67 · see citing works
“There is an association between diabetes and cancer [19,20] and clinical observations have highlighted metformin as a potential anti-cancer therapy [21].”
BackgroundBocci, F., Jolly, M. K., George, J. T., Levine, H., & Onuchic, J. N. (2018) · Oncotarget · doi:10.18632/oncotarget.25692 · Cited by 67 · see citing works
Vazquez-Martin, A., López-Bonetc, E., Cufí, S., Oliveras-Ferraros, C., Del Barco, S., Martin-Castillo, B., & Menendez, J. A. (2011) · Drug Resistance Updates · doi:10.1016/j.drup.2011.04.003 · Cited by 66 · see citing works
“…molecular explanations for the effects of metformin on the proliferation and survival of fully transformed BC cells (Ben Sahra et al., 2010b; Berstein, 2010; GonzalezAngulo and Meric-Bernstam, 2010; Jalving et al., 2010; Martin-Castillo et al., 2010b; Pollak, 2010; Vazquez-Martin et al., 2010a,b).”
BackgroundInfluentialTherapeutic Repurposing of Biguanides in Cancer
Zhao, H., Swanson, K. D., & Zheng, B. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.03.001 · Cited by 65 · see citing works
Campagnoli, C., Pasanisi, P., Abbà, C., Ambroggio, S., Biglia, N., Brucato, T., Colombero, R., Danese, S., Donadio, M., Venturelli, E., et al. (2012) · Clinical Breast Cancer · doi:10.1016/j.clbc.2012.03.004 · Cited by 65 · see citing works
The Use of Metformin and Colorectal Cancer Incidence in Patients with Type II Diabetes Mellitus
Smiechowski, B., Azoulay, L., Yin, H., Pollak, M., & Suissa, S. (2013) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-13-0196 · Cited by 64 · see citing works
“making it a safe andpromising chemopreventive agent for colorectal cancer (2, 23), it is unclear whether such results can be extrapolated at the populational level.”
BackgroundSelf-citationChaudhary, S. C., Kurundkar, D., Elmets, C. A., Kopelovich, L., & Athar, M. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01165.x · Cited by 64 · see citing works
Targeting the LKB1 Tumor Suppressor
Zhao, R., & Xu, Z. (2014) · Current Drug Targets · doi:10.2174/1389450114666140106095811 · Cited by 61 · see citing works
Cufí, S., Vázquez‐Martín, A., Oliveras‐Ferraros, C., Quirantes‐Piné, R., Segura‐Carretero, A., Micol, V., Joven, J., Bosch‐Barrera, J., Barco, S. D., Martı́n-Castillo, B., et al. (2012) · Cell Cycle · doi:10.4161/cc.11.6.19665 · Cited by 60 · see citing works
“because it may not have significant (if any) effects in non-diabetics individuals.(12-15) Because there is still a lack of retrospective clinical evidence for antitumor activity of metformin in nondiabetic individuals, strict criteria specifying high-risk populations in which metformin is expected to provide a greater…”
BackgroundDrug repurposing: Clinical practices and regulatory pathways
Saranraj, K., & Kiran, P. U. (2024) · Perspectives in Clinical Research · doi:10.4103/picr.picr_70_24 · Cited by 66 · see citing works
“…Sildenafil [40] Hypertension, angina Erectile dysfunction* Thalidomide [41] Sedative Multiple myeloma*, lepra reaction*, Behcet’s disease Metformin [42] Type 2 diabetes mellitus PCOS, anticancer, psoriasis Ivermectin [43] Antiparasitic Antiviral (COVID‑19), scabies Clozapine Schizophrenia…”
Westley, R., & May, F. E. B. (2013) · International Journal of Endocrinology · doi:10.1155/2013/632461 · Cited by 59 · see citing works
“Nonetheless, data are encouraging and suggest that further research into biguanides and their role in cancer protection is warranted [283].”
BackgroundMetformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer
Campagnoli, C., Berrino, F., Venturelli, E., Abbà, C., Biglia, N., Brucato, T., Cogliati, P., Danese, S., Donadio, M., Zito, G., et al. (2013) · Clinical Breast Cancer · doi:10.1016/j.clbc.2013.08.012 · Cited by 59 · see citing works
Repurposing old drugs to chemoprevention: the case of metformin
Heckman‐Stoddard, B. M., Gandini, S., Puntoni, M., Dunn, B. K., DeCensi, A., & Szabo, E. M. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.009 · Cited by 58 · see citing works
“In cancer cells, the consequences of this process include decreased protein synthesis, which correlates with reduced energy expenditure, and a decrease in cell proliferation [7,19].”
BackgroundInfluentialGerosuppressant Metformin: less is more
Menéndez, J. A., Cufí, S., Oliveras‐Ferraros, C., Vellón, L., Joven, J., & Vázquez‐Martín, A. (2011) · Aging · doi:10.18632/aging.100316 · Cited by 57 · see citing works
“Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report.”
BackgroundResultInfluentialChemoprevention Meets Glucose Control
Engelman, J. A., & Cantley, L. C. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0178 · Cited by 58 · see citing works
Taghizadehghalehjoughi, A., Hacımüftüoğlu, A., Çetin, M., Kaplan, A. B. U., Gălățeanu, B., Mezhuev, Y. O., Okkay, U., Taşpınar, N., Taşpınar, M., Uyanık, A., et al. (2018) · Nanomedicine · doi:10.2217/nnm-2017-0386 · Cited by 54 · see citing works
Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice
Zhang, Y., Xu, F. L., Liang, H., Cai, M., Wen, X., Li, X., & Weng, J. (2015) · Oncology Reports · doi:10.3892/or.2015.4476 · Cited by 52 · see citing works
“Thus, we preliminarily conclude that exenatide (exendin-4) inhibits endometrial cancer Ishikawa growth through phosphorylating AMPK through GLP-1R signaling, which is similar to the mechanism of metformin on endometrial cancer cells (7-9).”
Richards, K. A., Liou, J., Cryns, V. L., Downs, T. M., Abel, E. J., & Jarrard, D. F. (2018) · The Journal of Urology · doi:10.1016/j.juro.2018.06.031 · Cited by 52 · see citing works
NCI's provocative questions on cancer: some answers to ignite discussion
Blagosklonny, M. V. (2011) · Oncotarget · doi:10.18632/oncotarget.432 · Cited by 51 · see citing works
“Also metformin decreases the risk of cancer in humans [206, 211-220].”
BackgroundMetformin and Cancer Stem Cells: Old Drug, New Targets
Bednar, F., & Simeone, D. M. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-12-0026 · Cited by 51 · see citing works
“Metformin belongs to the biguanide class of antidiabetic drugs and is of emerging interest for cancer prevention and therapy (17).”
BackgroundMetformin as an energy restriction mimetic agent for breast cancer prevention
Thompson, H. J., Zhu, Z., Thompson, M., Jiang, W., & McGinley, J. N. (2011) · Journal of Carcinogenesis · doi:10.4103/1477-3163.83043 · Cited by 51 · see citing works
“As such, this work provides information about the potential use of metformin for breast cancer prevention in a population of women who do not experience either condition.[42,46] Nonetheless, the data reported may not adequately reflect the potential for metformin to prevent breast cancer in obese and/or diabetic women.”
BackgroundInfluentialLiu, Z., Ren, L., Liu, C., Xia, T., Zha, X., & Wang, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131207 · Cited by 50 · see citing works
“Biguanides, such as metformin and phenformin, are commonly used as therapeutics for type 2 diabetes[3].”
BackgroundMetformin: review of epidemiology and mechanisms of action in pancreatic cancer
Eibl, G., & Rozengurt, E. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09977-z · Cited by 48 · see citing works
AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?
Dandapani, M., & Hardie, D. G. (2013) · Biochemical Society Transactions · doi:10.1042/bst20120351 · Cited by 47 · see citing works
Singhal, J., Nagaprashantha, L. D., Vatsyayan, R., Awasthi, S., & Singhal, S. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024688 · Cited by 48 · see citing works
“Metformin (Glucophage) is a biguanide-class hypoglycemic agent that operates primarily through inhibition of AMPK (which regulates the rate of endocytosis), but is also linked with PPARc through PGC1a (PPARc-receptor co-activator) [22].”
BackgroundLea, M. A., Chacko, J., Bolikal, S., Hong, J. Y., Chung, R., Ortega, A., & desBordes, C. (2011) · PubMed · Cited by 47 · see citing works
- Authors
- Pollak, M.
- Affiliations
- Author's Affiliation: Department of Oncology, McGill University and Jewish General Hospital, Montreal, Quebec, Canada
- Venue
- Cancer Prevention Research
- Published
- 2010-09-01
- Volume
- 3
- Issue
- 9
- Pages
- 1060-1065
- ISSN
- 1940-6207 (ISSN-L)
- 1940-6215
- PMC
- PMC2954412
- OpenAlex
- W2165189414
- Cited by
- 240
- References
- 56
- Citations by year
- 2026: 12 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 12 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 23 · 2014: 14 · 2013: 23 · 2012: 44
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Prevention Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Prostate Cancer Foundation
- McGill University
- Prostate Cancer Canada
- National Institutes of Health (5r01ca101008-02)
- Canadian Cancer Society Research Institute
- National Cancer Institute (R01 CA101008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- metformin, biguanides, chemoprevention, cancer therapy, diabetes mellitus, mechanism of action, clinical trial design, laboratory model
- MeSH terms
- Animals, Antineoplastic Agents, Biguanides, Humans, Hypoglycemic Agents, Medical Oncology, Metformin, Neoplasms, Biomedical Research
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