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Understanding the benefit of metformin use in cancer treatment

Ryan JO Dowling, Pamela J Goodwin, Vuk Stambolic

BMC Medicine · 2011 · Review

doi:10.1186/1741-7015-9-33

Abstract

Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 18, 2026. Paragraph numbers are ours, so an answer can point at one.

A brief history of biguanides

The biguanides metformin, phenformin and buformin are derived from the herb Galega officinalis (French lilac, also known as Goat's Rue or Italian Fitch) and were originally developed for the treatment of hyperglycemia and type 2 diabetes. Use of tea infused with French lilac for relief of frequent urination (polyuria) and halitosis (a sweet odor on breath), both now well known symptoms of diabetes, dates back to ancient Egypt and medieval Europe. Work in the 1920 s identified biguanides as the active compounds from the French lilac and led to their development as therapeutics in the 1950 s. While phenformin and buformin were withdrawn from the market in the 1970 s due to toxicity related to lactic acidosis, metformin (N',N'-dimethylbiguanide) remains one of the most commonly prescribed drugs, with nearly 120 million prescriptions filled yearly worldwide. Metformin was approved for the treatment of hyperglycemia in Britain in 1958, Canada in 1972, and the US in 1995. In addition to its use in diabetics, metformin is also effective in the treatment of polycystic ovary syndrome and is being explored as an antiviral and anticancer agent. Indeed, the use of biguanides in oncology was originally initiated in a series of studies targeting altered metabolism in non-diabetic cancer patients. More recently, metformin has been associated with decreased cancer incidence and mortality in diabetic patients and the insulin-lowering effects of metformin may be integral to its anticancer properties. Here, we discuss the use of metformin in oncology and its potential mechanisms of action in the inhibition of cancer.

Mechanism of metformin action

At the cellular level, metformin activates AMP-activated protein kinase (AMPK), an energy sensor involved in regulating cellular metabolism that is activated by increases in the intracellular levels of AMP. Metformin indirectly activates AMPK by disrupting complex I of the mitochondrial respiratory chain, which leads to decreased ATP synthesis and a rise in the cellular AMP:ATP ratio. Increased association of AMPK with AMP under such conditions leads to stimulation of AMPK activity by three mechanisms. AMP allosterically activates AMPK and facilitates phosphorylation of its catalytic subunit on residue Thr172 by the upstream kinase liver kinase B1 (LKB1, also known as STK11), the protein product of the tumor suppressor gene mutated in the Peutz-Jeghers cancer predisposition syndrome. Binding of AMP to AMPK also prevents dephosphorylation of AMPK Thr172 by protein phosphatases. Activated AMPK phosphorylates a number of downstream targets leading to stimulation of catabolic processes that generate ATP, such as fatty acid β-oxidation and glycolysis, and suppression of many of the processes dependent on ample cellular ATP supply, including gluconeogenesis, protein and fatty acid synthesis and cholesterol biosynthesis.

The mechanism of metformin action in the treatment of diabetes involves the inhibition of hepatic gluconeogenesis and the stimulation of glucose uptake in muscle. These effects are achieved by AMPK-mediated transcriptional regulation of genes involved in gluconeogenesis in the liver and those encoding glucose transporters in the muscle, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and glucose transporter type 4 (GLUT4), respectively. Consequently, metformin enhances insulin sensitivity and lowers fasting blood glucose and insulin in diabetics.

Metformin and cancer

The potential for application of metformin in oncology was first recognized in retrospective epidemiological studies of diabetic patients with cancer. Numerous observational studies reported decreased cancer incidence and cancer-related mortality in diabetics receiving standard doses of metformin (1500 to 2250 mg/day in adults). For example, Evans and colleagues reported a reduced risk of subsequent cancer diagnosis in diabetics receiving metformin (vs those patients not receiving the drug), with the protective effect increasing with greater metformin exposure. Additional studies examining all forms of cancer have reported reduced cancer risk in diabetics on metformin (vs no metformin treatment) and lower cancer-related mortality in patients receiving metformin compared to those receiving other standard diabetic therapies. Furthermore, a recent epidemiological study of 2,529 women with breast cancer reported higher pathologic complete response rates (pCRs; considered a surrogate for overall survival in this setting) to neoadjuvant systemic therapy in diabetic patients receiving metformin (pCR 24%) compared to diabetic patients not receiving metformin (pCR 8%) and non-diabetic patients not receiving metformin (pCR 16%). However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate in this study. Moreover, in a similar study of diabetic prostate cancer patients, metformin use was not associated with benefit. Thus, further clinical research is needed to fully appreciate the impact of metformin on cancer recurrence and survival.

While the majority of evidence supporting a role for metformin in the treatment of cancer has been derived from retrospective studies involving diabetics, some prospective clinical trials have been completed in non-diabetic patients. In a recent study, low doses of metformin (250 mg/day) reduced the number of rectal aberrant crypt foci (a surrogate marker for colorectal cancer) and decreased the proliferative activity of colonic epithelium in non-diabetic patients. Furthermore, interim analyses of ongoing studies involving neoadjuvant metformin treatment of newly diagnosed breast cancer patients have demonstrated that metformin is safe and well tolerated, and exhibits favorable effects on insulin metabolism and tumor cell proliferation and apoptosis.

Metformin also displays significant growth inhibitory effects in several cancer cell and mouse tumor models. In cell culture, metformin inhibits the proliferation of a range of cancer cells including breast, prostate, colon, endometrial, ovarian, and glioma. The effects of metformin on cancer cell proliferation were associated with AMPK activation, reduced mammalian target of rapamycin (mTOR) signaling and protein synthesis, as well as a variety of other responses including decreased epidermal growth factor receptor (EGFR), Src, and mitogen-activated protein kinase (MAPK) activation, decreased expression of cyclins, and increased expression of p27. While not universally observed in all cells, metformin has been found to induce apoptosis in certain cell lines derived from endometrial cancers, glioma, and triple negative breast tumors.

Recent studies have demonstrated that metformin may also target cancer-initiating cells. For example, metformin inhibited the growth of a subpopulation of breast cancer cells shown to have such property in culture and reduced their ability to form tumors in mice and when combined with trastuzumab, metformin reduced the cancer-initiating cell population in Her2-amplified breast cancer cells. Interestingly, metformin may also be involved in regulating breast cancer-initiating cell ontogeny by transcriptionally repressing the process of epithelial to mesenchymal transition (EMT). Metformin also reduced the growth of a variety of tumor xenografts in mice including those established from breast and prostate cancer cells, and suppressed the development of breast, colon and other tumors in transgenic mice. In addition, metformin inhibited the development of chemically induced lung tumors and preneoplastic colonic lesions in mice.

Mechanism of action in cancer

The anticancer effects of metformin are associated with both direct (insulin- independent) and indirect (insulin-dependent) actions of the drug (Figure 1). The indirect, insulin-dependent effects of metformin are mediated by the ability of AMPK to inhibit the transcription of key gluconeogenesis genes in the liver and stimulate glucose uptake in muscle, thus reducing fasting blood glucose and insulin. The insulin-lowering effects of metformin may play a major role in its anticancer activity since insulin has mitogenic and prosurvival effects and tumor cells often express high levels of the insulin receptor, indicating a potential sensitivity to the growth promoting effects of the hormone. Further, obesity and high insulin levels are adverse prognostic factors for a number of cancers particularly those of the breast, prostate and colon. Consequently, metformin may diminish the negative effects of insulin on tumor development and growth. Indeed, metformin suppressed the stimulatory effects of obesity and hyperinsulinemia on lung tumor growth in mice by improving insulin sensitivity, lowering circulating insulin, and activating AMPK signaling. In addition, metformin reduced circulating insulin levels by 22% and improved insulin sensitivity by 25% in non-diabetic women with breast cancer, highlighting the insulin-lowering effects of metformin as a potential mechanism of action in the treatment of breast cancer.

The direct, insulin-independent effects of metformin originate from LKB1-mediated activation of AMPK and a reduction in mTOR signaling and protein synthesis in cancer cells (Figure 1). AMPK impacts mTOR via phosphorylation and activation of the tumor suppressor tuberous sclerosis complex 2 (TSC2, tuberin), which negatively regulates mTOR activity. mTOR is a key integrator of growth factor and nutrient signals and is a critical mediator of the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3K/PKB/Akt) signaling pathway, which is one of the most frequently deregulated molecular networks in human cancer. Metformin-mediated AMPK activation leads to an inhibition of mTOR signaling, a reduction in phosphorylation of its major downstream effectors, the eukaryotic initiation factor 4E-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks), and an inhibition of global protein synthesis and proliferation in a number of different cancer cell lines.

Some recent reports raise the possibility that metformin may mediate additional anticancer effects independently of AMPK, LKB1, and TSC2. Indeed, metformin reduced mTOR signaling independently of AMPK and TSC2 by inhibiting Rag GTPase-mediated activation of mTOR. Paradoxically, at least in one cell model system, loss of function of LKB1 sensitized cells to the inhibitory effects of metformin under conditions of low glucose. Moreover, metformin reduced hepatic gluconeogenesis by lowering hepatic energy levels in the absence of AMPK and LKB1. While these additional effects are intriguing, LKB1-dependent suppression of mTOR signaling remains the key candidate mechanism of antitumor action of metformin.

Conclusions and future work with metformin in cancer

The clinical safety, well characterized pharmacodynamic profile, and low cost of metformin make it an ideal candidate for development as an anticancer agent. The recent convergence of epidemiologic, clinical and preclinical evidence supporting a potential anticancer effect of metformin has led to an explosion of interest in evaluating this agent in human cancer. However, a number of issues need further consideration in the development of metformin as a cancer therapy. In particular, the retrospective epidemiological studies that first identified the potential anticancer effects of metformin are difficult to confirm and contain only diabetic patient populations. While cell culture and mouse models have been integral to the characterization of the mechanism of action of metformin in the inhibition of cancer, they are artificial and rely on non-physiological doses of metformin in the presence of excess insulin and growth factors. New, more physiologically relevant in vitro models will be required to fully elucidate the mechanism of action of metformin (both the insulin-dependent and insulin-independent actions) and inform clinical studies. Furthermore, additional research is required to identify key patient and tumor factors that govern metformin sensitivity, which is critical for the design of clinical trials and the identification of patients best suited for metformin treatment. Current preclinical and clinical knowledge of metformin action suggest that patients exhibiting hyperinsulinemia and tumors expressing the insulin receptor, LKB1, and TSC2 would benefit most from metformin therapy, while patients with normal circulating insulin levels and tumors lacking expression of the insulin receptor, LKB1, and TSC2 would likely be unresponsive to the drug. Predicting how non-diabetic patients will respond to metformin and differentiating between its direct and indirect effects may be challenging. However, the initiation of new, focused clinical trials containing strong correlative science components will be crucial in understanding the effects of the drug on a range of cancer patients (including non-diabetic patients) and the identification of biomarkers that predict metformin benefit and response to therapy. Currently, a number of clinical trials examining the use of metformin as a cancer therapy are underway including studies in prostate, breast, endometrial and pancreatic cancer patients. In fact, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has initiated a large phase III clinical trial (NCIC CTG MA.32) examining the effect of metformin versus placebo in over 3,500 women with early stage breast cancer. Coupled with the implementation of new preclinical models, these clinical trials will be integral to the development and effective use of metformin as a potential anticancer therapy.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

RD, PG and VS wrote the paper. All authors read and approved the final manuscript.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1741-7015/9/33/prepub

References 62

  1. 1.

    Witters LA The blooming of the French lilacJ Clin Invest2001 10811051107

    Not in our library10.1172/jci14178

  2. 2.

    Hadden DR Goat's rue - French lilac - Italian fitch - Spanish sainfoin: gallega officinalis and metformin: the Edinburgh connectionJ R Coll Physicians Edinb2005 35258260

    Not in our library

  3. 3.

    Bailey CJ Day C Metformin: its botanical backgroundPract Diab Int2004 21115117

    Not in our library10.1002/pdi.606

  4. 4.

    Bailey CJ Turner RC MetforminN Engl J Med1996 334574579

    Not in our library10.1056/nejm199602293340906

  5. 5.

    Ben Sahra I Le Marchand-Brustel Y Tanti JF Bost F Metformin in cancer therapy: a new perspective for an old antidiabetic drug?Mol Cancer Ther2010 910921099

    Not in our library10.1158/1535-7163.mct-09-1186

  6. 6.

    Diamanti-Kandarakis E Economou F Palimeri S Christakou C Metformin in polycystic ovary syndromeAnn N Y Acad Sci1205192198

    Not in our library10.1111/j.1749-6632.2010.05679.x

  7. 7.

    Rotella CM Monami M Mannucci E Metformin beyond diabetes: new life for an old drugCurr Diabetes Rev2006 2307315

    Not in our library10.2174/157339906777950651

  8. 8.

    Dilman VM Berstein LM Ostroumova MN Fedorov SN Poroshina TE Tsyrlina EV Buslaeva VP Semiglazov VF Seleznev IK Bobrov YuF Vasilyeva IA Kondratjev VB Nemirovsky VS Nikiforov YF Metabolic immunodepression and metabolic immunotherapy: an attempt of improvement in immunologic response in breast cancer patients by correction of metabolic disturbancesOncology1982 391319

    Not in our library10.1159/000225596

  9. 9.

    Dilman VM Berstein LM Yevtushenko TP Tsyrlina YV Ostroumova MN Bobrov Yu F Revskoy S Kovalenko IG Simonov NN Preliminary evidence on metabolic rehabilitation of cancer patientsArch Geschwulstforsch1988 58175183

    Not in our library

  10. 10.

    Berstein LM Modern approach to metabolic rehabilitation of cancer patients: biguanides (phenformin and metformin) and beyondFuture Oncol2010 613131323

    Not in our library10.2217/fon.10.87

  11. 11.

    Evans JM Donnelly LA Emslie-Smith AM Alessi DR Morris AD Metformin and reduced risk of cancer in diabetic patientsBMJ2005 33013041305

    Not in our library10.1136/bmj.38415.708634.f7

  12. 12.

    Goodwin PJ Pritchard KI Ennis M Clemons M Graham M Fantus IG Insulin-lowering effects of metformin in women with early breast cancerClin Breast Cancer2008 8501505

    Not in our library10.3816/cbc.2008.n.060

  13. 13.

    Algire C Zakikhani M Blouin MJ Shuai JH Pollak M Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growthEndocr Relat Cancer2008 15833839

    Not in our library10.1677/erc-08-0038

  14. 14.

    Kahn BB Alquier T Carling D Hardie DG AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolismCell Metab2005 11525

    Not in our library10.1016/j.cmet.2004.12.003

  15. 15.

    Zhou G Myers R Li Y Chen Y Shen X Fenyk-Melody J Wu M Ventre J Doebber T Fujii N Musi N Hirshman MF Goodyear LJ Moller DE Role of AMP-activated protein kinase in mechanism of metformin actionJ Clin Invest2001 10811671174

    Not in our library10.1172/jci13505

  16. 16.

    El-Mir MY Nogueira V Fontaine E Averet N Rigoulet M Leverve X Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex IJ Biol Chem2000 275223228

    Not in our library10.1074/jbc.275.1.223

  17. 17.

    Shaw RJ Kosmatka M Bardeesy N Hurley RL Witters LA DePinho RA Cantley LC The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stressProc Natl Acad Sci USA2004 10133293335

    Not in our library10.1073/pnas.0308061100

  18. 18.

    Hardie DG AMP-activated/SNF1 protein kinases: conserved guardians of cellular energyNat Rev Mol Cell Biol2007 8774785

    Not in our library10.1038/nrm2249

  19. 19.

    Towler MC Hardie DG AMP-activated protein kinase in metabolic control and insulin signalingCirc Res2007 100328341

    Not in our library10.1161/01.res.0000256090.42690.05

  20. 20.

    Cusi K Consoli A DeFronzo RA Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitusJ Clin Endocrinol Metab1996 8140594067

    Not in our library10.1210/jc.81.11.4059

  21. 21.

    Hundal RS Krssak M Dufour S Laurent D Lebon V Chandramouli V Inzucchi SE Schumann WC Petersen KF Landau BR Shulman GI Mechanism by which metformin reduces glucose production in type 2 diabetesDiabetes2000 4920632069

    Not in our library10.2337/diabetes.49.12.2063

  22. 22.

    Shaw RJ Lamia KA Vasquez D Koo SH Bardeesy N Depinho RA Montminy M Cantley LC The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metforminScience2005 31016421646

    Not in our library10.1126/science.1120781

  23. 23.

    Hardie DG The AMP-activated protein kinase pathway--new players upstream and downstreamJ Cell Sci2004 11754795487

    Not in our library10.1242/jcs.01540

  24. 24.

    Libby G Donnelly LA Donnan PT Alessi DR Morris AD Evans JM New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetesDiabetes Care2009 3216201625

    Not in our library10.2337/dc08-2175

  25. 25.

    Decensi A Puntoni M Goodwin P Cazzaniga M Gennari A Bonanni B Gandini S Metformin and cancer risk in diabetic patients: a systematic review and meta-analysisCancer Prev Res (Phila)2010 314511461

    Not in our library10.1158/1940-6207.capr-10-0157

  26. 26.

    Landman GW Kleefstra N van Hateren KJ Groenier KH Gans RO Bilo HJ Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16Diabetes Care2010 33322326

    Not in our library10.2337/dc09-1380

  27. 27.

    Monami M Lamanna C Balzi D Marchionni N Mannucci E Sulphonylureas and cancer: a case-control studyActa Diabetol2009 46279284

    Not in our library10.1007/s00592-008-0083-2

  28. 28.

    Bowker SL Majumdar SR Veugelers P Johnson JA Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulinDiabetes Care2006 29254258

    Not in our library10.2337/diacare.29.02.06.dc05-1558

  29. 29.

    Jiralerspong S Palla SL Giordano SH Meric-Bernstam F Liedtke C Barnett CM Hsu L Hung MC Hortobagyi GN Gonzalez-Angulo AM Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancerJ Clin Oncol2009 2732973302

    Not in our library10.1200/jco.2009.19.6410

  30. 30.

    Patel T Hruby G Badani K Abate-Shen C McKiernan JM Clinical outcomes after radical prostatectomy in diabetic patients treated with metforminUrology7612401244

    Not in our library10.1016/j.urology.2010.03.059

  31. 31.

    Hosono K Endo H Takahashi H Sugiyama M Sakai E Uchiyama T Suzuki K Iida H Sakamoto Y Yoneda K Koide T Tokoro C Abe Y Inamori M Nakagama H Nakajima A Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trialCancer Prev Res (Phila)2010 310771083

    Not in our library10.1158/1940-6207.capr-10-0186

  32. 32.

    Niraula S Stambolic V Dowling RJO Ennis M Chang MC Done SJ Hallak S Hood N Goodwin PJ Clinical and biologic effects of metformin in early stage breast cancerCancer Res2010 7024, Suppl104sAbs No. PD03-06

    Not in our library

  33. 33.

    Hadad SM Dewar JA Elseedawy E Jordan LB Purdie C Bray SE Thompson AM Gene Signature of metformin actions on primary breast cancer within a window of opportunity randomized clinical trialJ Clin Oncol2010 28Suppl560

    Not in our library

  34. 34.

    Dowling RJ Zakikhani M Fantus IG Pollak M Sonenberg N Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cellsCancer Res2007 671080410812

    Not in our library10.1158/0008-5472.can-07-2310

  35. 35.

    Zakikhani M Dowling R Fantus IG Sonenberg N Pollak M Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cellsCancer Res2006 661026910273

    Not in our library10.1158/0008-5472.can-06-1500

  36. 36.

    Ben Sahra I Laurent K Loubat A Giorgetti-Peraldi S Colosetti P Auberger P Tanti JF Le Marchand-Brustel Y Bost F The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 levelOncogene2008 2735763586

    Not in our library10.1038/sj.onc.1211024

  37. 37.

    Buzzai M Jones RG Amaravadi RK Lum JJ DeBerardinis RJ Zhao F Viollet B Thompson CB Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growthCancer Res2007 6767456752

    Not in our library10.1158/0008-5472.can-06-4447

  38. 38.

    Cantrell LA Zhou C Mendivil A Malloy KM Gehrig PA Bae-Jump VL Metformin is a potent inhibitor of endometrial cancer cell proliferation--implications for a novel treatment strategyGynecol Oncol1169298

    Not in our library10.1016/j.ygyno.2009.09.024

  39. 39.

    Isakovic A Harhaji L Stevanovic D Markovic Z Sumarac-Dumanovic M Starcevic V Micic D Trajkovic V Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosisCell Mol Life Sci2007 6412901302

    Not in our library10.1007/s00018-007-7080-4

  40. 40.

    Gotlieb WH Saumet J Beauchamp MC Gu J Lau S Pollak MN Bruchim I In vitro metformin anti-neoplastic activity in epithelial ovarian cancerGynecol Oncol2008 110246250

    Not in our library10.1016/j.ygyno.2008.04.008

  41. 41.

    Liu B Fan Z Edgerton SM Deng XS Alimova IN Lind SE Thor AD Metformin induces unique biological and molecular responses in triple negative breast cancer cellsCell Cycle2009 820312040

    Not in our library10.4161/cc.8.13.8814

  42. 42.

    Hirsch HA Iliopoulos D Tsichlis PN Struhl K Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remissionCancer Res2009 6975077511

    Not in our library10.1158/0008-5472.can-09-2994

  43. 43.

    Vazquez-Martin A Oliveras-Ferraros C Barco SD Martin-Castillo B Menendez JA The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cellsBreast Cancer Res Treat2011 in press

    Not in our library10.1007/s10549-010-0924-x

  44. 44.

    Vazquez-Martin A Oliveras-Ferraros C Cufi S Del Barco S Martin-Castillo B Menendez JA Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) statusCell Cycle2010 938073814

    Not in our library10.4161/cc.9.18.13131

  45. 45.

    Anisimov VN Berstein LM Egormin PA Piskunova TS Popovich IG Zabezhinski MA Kovalenko IG Poroshina TE Semenchenko AV Provinciali M Re F Franceschi C Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic miceExp Gerontol2005 40685693

    Not in our library10.1016/j.exger.2005.07.007

  46. 46.

    Tomimoto A Endo H Sugiyama M Fujisawa T Hosono K Takahashi H Nakajima N Nagashima Y Wada K Nakagama H Nakajima A Metformin suppresses intestinal polyp growth in ApcMin/+ miceCancer Sci2008 9921362141

    Not in our library10.1111/j.1349-7006.2008.00933.x

  47. 47.

    Memmott RM Mercado JR Maier CR Kawabata S Fox SD Dennis PA Metformin prevents tobacco carcinogen--induced lung tumorigenesisCancer Prev Res (Phila)2010 310661076

    Not in our library10.1158/1940-6207.capr-10-0055

  48. 48.

    Hosono K Endo H Takahashi H Sugiyama M Uchiyama T Suzuki K Nozaki Y Yoneda K Fujita K Yoneda M Inamori M Tomatsu A Chihara T Shimpo K Nakagama H Nakajima A Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinaseMol Carcinog2010 49662671

    Not in our library10.1002/mc.20637

  49. 49.

    Belfiore A Frasca F IGF and insulin receptor signaling in breast cancerJ Mammary Gland Biol Neoplasia2008 13381406

    Not in our library10.1007/s10911-008-9099-z

  50. 50.

    Frasca F Pandini G Sciacca L Pezzino V Squatrito S Belfiore A Vigneri R The role of insulin receptors and IGF-I receptors in cancer and other diseasesArch Physiol Biochem2008 1142337

    Not in our library10.1080/13813450801969715

  51. 51.

    Mulligan AM O'Malley FP Ennis M Fantus IG Goodwin PJ Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancerBreast Cancer Res Treat2007 1063947

    Not in our library10.1007/s10549-006-9471-x

  52. 52.

    Ish-Shalom D Christoffersen CT Vorwerk P Sacerdoti-Sierra N Shymko RM Naor D De Meyts P Mitogenic properties of insulin and insulin analogues mediated by the insulin receptorDiabetologia1997 40Suppl 2S2531

    Not in our library10.1007/s001250051393

  53. 53.

    Basen-Engquist K Chang M Obesity and cancer risk: recent review and evidenceCurr Oncol Rep2011 137176

    Not in our library10.1007/s11912-010-0139-7

  54. 54.

    Goodwin PJ Ennis M Pritchard KI Trudeau ME Koo J Madarnas Y Hartwick W Hoffman B Hood N Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort studyJ Clin Oncol2002 204251

    Not in our library10.1200/jco.20.1.42

  55. 55.

    Inoki K Zhu T Guan KL TSC2 mediates cellular energy response to control cell growth and survivalCell2003 115577590

    Not in our library10.1016/s0092-8674(03)00929-2

  56. 56.

    Lee JW Soung YH Kim SY Lee HW Park WS Nam SW Kim SH Lee JY Yoo NJ Lee SH PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomasOncogene2005 2414771480

    Not in our library10.1038/sj.onc.1208304

  57. 57.

    Markman B Atzori F Perez-Garcia J Tabernero J Baselga J Status of PI3K inhibition and biomarker development in cancer therapeuticsAnn Oncol2010 21683691

    Not in our library10.1093/annonc/mdp347

  58. 58.

    Alimova IN Liu B Fan Z Edgerton SM Dillon T Lind SE Thor AD Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitroCell Cycle2009 8909915

    Not in our library10.4161/cc.8.6.7933

  59. 59.

    Kalender A Selvaraj A Kim SY Gulati P Brûlé S Viollet B Kemp BE Bardeesy N Dennis P Schlager JJ Marette A Kozma SC Thomas G Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent mannerCell Metab2010 11390401

    Not in our library10.1016/j.cmet.2010.03.014

  60. 60.

    Foretz M Hebrard S Leclerc J Zarrinpashneh E Soty M Mithieux G Sakamoto K Andreelli F Viollet B Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy stateJ Clin Invest2010 12023552369

    Not in our library10.1172/jci40671

  61. 61.

    Algire C Amrein L Bazile M David S Zakikhani M Pollak M Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivoOncogene2011 3011741182

    Not in our library10.1038/onc.2010.483

  62. 62.

    Goodwin PJ Stambolic V Lemieux J Chen BE Parulekar WR Gelmon KA Hershman DL Hobday TJ Ligibel JA Mayer IA Pritchard KI Whelan TJ Rastogi P Shepherd LE Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agentsBreast Cancer Res Treat2011 126215220

    Not in our library10.1007/s10549-010-1224-1

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