metformin and Ovarian Neoplasms studies

Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.

Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.

Research Excerpts

Excerpt	Relevance	Reference
"To evaluate the efficacy of metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer."	9.30	Metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer: a prospective open-label pilot trial. ( Liu, Y; Sun, H; Zhang, H; Zheng, Y; Zhu, J, 2019)
"This study examined the effect of combination treatment with the poly (ADP-ribose) polymerase inhibitor olaparib and metformin on homologous recombination (HR)-proficient epithelial ovarian cancer (EOC)."	8.02	Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines. ( Gajek, A; Gralewska, P; Marczak, A; Rogalska, A, 2021)
"Antimetastatic effect of Metformin has been documented in epithelial ovarian cancer (EOC)."	8.02	Roles of metformin-mediated girdin expression in metastasis of epithelial ovarian cancer. ( Dang, J; Gao, J; Hu, D; Jin, Z; Li, L; Li, W; Liu, X; Luo, Y; Ma, F; Sun, H; Wang, D; Wang, J, 2021)
"These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis."	7.96	Metformin Abrogates Age-Associated Ovarian Fibrosis. ( Allen, CH; Azzi, F; Boyd, RW; Cook, DP; Forsyth, A; Gray, DA; Kelly, BS; Lo, B; McCloskey, CW; Murugkar, S; Rayner, KJ; Senterman, MK; Trudel, D; Upham, J; Vanderhyden, BC, 2020)
" Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo."	7.80	Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation. ( Berek, JS; Chung, YM; Guan, M; Hu, MC; Hu, T; Ma, J; Ma, M, 2014)
"The aims of the study were to evaluate the ability of metformin to induce apoptosis in epithelial ovarian cancer cell lines and to identify the pathways involved in this effect."	7.77	Induction of apoptosis by metformin in epithelial ovarian cancer: involvement of the Bcl-2 family proteins. ( Beauchamp, MC; Gotlieb, WH; Piura, E; Pollak, M; Segal, E; Yasmeen, A, 2011)
"Metformin could inhibit the expression of CCNE1, which is associated with the anti-proliferative effect of tumor cells."	5.91	CCNE1 is a potential target of Metformin for tumor suppression of ovarian high-grade serous carcinoma. ( Chu, TY; Huang, HS; Liou, YL; Mei, J; Tian, H; Wang, J; Wu, N; Zhang, W, 2023)
"Metformin has long been an attractive therapeutic option for EwS, but hypoxia limits its efficacy."	5.56	Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways. ( Cheng, H; Lau, CC; Nan, X; Qiu, B; Sheng, J; Wang, J; Wong, STC; Yin, Z; Yustein, JT; Zhao, H, 2020)
"In all, 303 women were diagnosed with ovarian cancer during the follow up."	5.48	The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study. ( Arffman, M; Arima, R; Hautakoski, A; Hinkula, M; Ilanne-Parikka, P; Kangaskokko, J; Läärä, E; Marttila, M; Puistola, U; Sund, R; Urpilainen, E, 2018)
"Metformin was demonstrated to evoke metabolic stress and induce cancer cell death."	5.48	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3). ( Bryś, M; Forma, E; Marczak, A; Rogalska, A; Śliwińska, A, 2018)
"High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy."	5.48	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells. ( Bukowska, B; Marczak, A; Rogalska, A, 2018)
"When metformin was combined with carboplatin or paclitaxel, an increased apoptotic activity was observed, implicating a chemo-adjuvant potential."	5.42	Metformin and epithelial ovarian cancer therapeutics. ( Kumar, L; Patel, S; Singh, N, 2015)
"In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs."	5.42	Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer. ( Eckert, MA; Johnson, A; Lengyel, E; Litchfield, LM; Mills, KA; Mukherjee, A; Pan, S; Romero, IL; Shridhar, V, 2015)
"To evaluate the efficacy of metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer."	5.30	Metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer: a prospective open-label pilot trial. ( Liu, Y; Sun, H; Zhang, H; Zheng, Y; Zhu, J, 2019)
"This study examined the effect of combination treatment with the poly (ADP-ribose) polymerase inhibitor olaparib and metformin on homologous recombination (HR)-proficient epithelial ovarian cancer (EOC)."	4.02	Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines. ( Gajek, A; Gralewska, P; Marczak, A; Rogalska, A, 2021)
"Antimetastatic effect of Metformin has been documented in epithelial ovarian cancer (EOC)."	4.02	Roles of metformin-mediated girdin expression in metastasis of epithelial ovarian cancer. ( Dang, J; Gao, J; Hu, D; Jin, Z; Li, L; Li, W; Liu, X; Luo, Y; Ma, F; Sun, H; Wang, D; Wang, J, 2021)
"These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis."	3.96	Metformin Abrogates Age-Associated Ovarian Fibrosis. ( Allen, CH; Azzi, F; Boyd, RW; Cook, DP; Forsyth, A; Gray, DA; Kelly, BS; Lo, B; McCloskey, CW; Murugkar, S; Rayner, KJ; Senterman, MK; Trudel, D; Upham, J; Vanderhyden, BC, 2020)
" Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo."	3.80	Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation. ( Berek, JS; Chung, YM; Guan, M; Hu, MC; Hu, T; Ma, J; Ma, M, 2014)
"The aims of the study were to evaluate the ability of metformin to induce apoptosis in epithelial ovarian cancer cell lines and to identify the pathways involved in this effect."	3.77	Induction of apoptosis by metformin in epithelial ovarian cancer: involvement of the Bcl-2 family proteins. ( Beauchamp, MC; Gotlieb, WH; Piura, E; Pollak, M; Segal, E; Yasmeen, A, 2011)
"Metformin-treated tumors, compared with historical controls, were evaluated for CSC number and chemotherapy response."	2.94	Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer. ( Bregenzer, M; Brown, JR; Buckanovich, RJ; Cabrera, L; Chan, DK; Coffman, LG; Fan, H; Griffith, KA; Johnston, C; Liu, JR; McLean, K; Mehta, G; Mehta, P; Modugno, F; Orr, BC; Reynolds, RK; Shank, JJ; Shen, H; Szulawski, R; Taylor, SE; Uppal, S; Yang, K, 2020)
"Epithelial ovarian cancer has poor outcomes with standard therapy and limited options for treatment of recurrent disease."	2.82	Use of "Repurposed" Drugs in the Treatment of Epithelial Ovarian Cancer: A Systematic Review. ( Dubashi, B; Ganesan, P; Goenka, L; Selvarajan, S, 2022)
"Metformin is a hypoglycemic agent that is commonly used for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease."	2.82	Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings. ( Tossetta, G, 2022)
"An otherwise untreated rectal cancer, progressing over 3 years, regressed after severe toxic dermatitis lasting over one week."	2.72	Immunology of tissue homeostasis, ovarian cancer growth and regression, and long lasting cancer immune prophylaxis - review of literature. ( Bukovsky, A, 2021)
"Statin use is associated with better ovarian cancer survival but further study, preferably a clinical trial, is required."	2.66	Common medications and survival in women with ovarian cancer: A systematic review and meta-analysis. ( Dixon-Suen, S; Jordan, SJ; Majidi, A; Na, R; Webb, PM, 2020)
"The main challenge in ovarian cancer treatment is the management of recurrences."	2.66	Recycling the Purpose of Old Drugs to Treat Ovarian Cancer. ( Bartosch, C; Henriques Abreu, M; Nunes, M; Ricardo, S, 2020)
"Metformin was not associated with improved overall survival (HR=0."	2.61	No Effect of Metformin on Ovarian Cancer Survival: A Systematic Review and Meta-Analysis of Cohort Studies. ( Bi, Y; Liu, X; Liu, Y; Wang, Y; Yan, P; Zhang, ZJ, 2019)
"Ovarian cancer is the seventh most common cancer and the eighth most common cause of cancer mortality in women."	2.61	Current state and outlook for drug repositioning anticipated in the field of ovarian cancer. ( Aoki, D; Banno, K; Kobayashi, Y; Kunitomi, H; Tominaga, E, 2019)
"The pooled OR for ovarian cancer occurrence and mortality comparing metformin use with non-use or use of other hypoglycemic drugs was 0."	2.61	Association of metformin use with ovarian cancer incidence and prognosis: a systematic review and meta-analysis. ( Liu, B; Shi, J; Wang, H; Yang, L; Zhang, T, 2019)
"Salinomycin is an antibiotic isolated from Streptomyces albus bacteria."	2.58	Ovarian cancer stem cells: A target for oncological therapy. ( Huczyński, A; Markowska, A; Markowska, J; Rehlis, S; Sajdak, S, 2018)
"Failure in ovarian cancer therapy, following cytoreduction and chemotherapy, is related to the presence of cancer stem cells - a small subpopulation of cells resistant to chemotherapy and irradiation - in the tumour which may cause cancer relapse and manifestation of metastases."	2.55	Angiogenesis and cancer stem cells: New perspectives on therapy of ovarian cancer. ( Huczyński, A; Markowska, A; Markowska, J; Sajdak, S, 2017)
"Ovarian cancer is the most lethal gynecological malignancy."	2.52	[Novel strategies of ovarian cancer treatment]. ( Boratyn-Nowicka, A; Cholewa, H; Duda, K; Okopień, B; Łabuzek, K, 2015)
"Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells."	2.50	Metformin against cancer stem cells through the modulation of energy metabolism: special considerations on ovarian cancer. ( Kim, MK; Kim, TH; Song, YS; Suh, DH, 2014)
"Metformin is a biguanide drug, typically used for diabetes treatment, currently being studied to evaluate its role in the treatment and prevention of gynecologic cancers."	2.50	Metformin and gynecologic cancers. ( Bae-Jump, V; Stine, JE, 2014)
"Key words included "metformin" AND ("ovarian cancer" OR "ovary tumor")."	2.49	The effects of metformin on ovarian cancer: a systematic review. ( Chaiyakunapruk, N; Dilokthornsakul, P; Pratoomsoot, C; Saokaew, S; Sruamsiri, R; Termrungruanglert, W, 2013)
"Obesity is a known risk factor for many types of cancers and a number of endocrine factors, including adipokines and steroid hormones, are regulated by and regulate AMPK."	2.49	Endocrine-related cancers and the role of AMPK. ( Brown, KA; Samarajeewa, NU; Simpson, ER, 2013)
"Metformin was found to increase the dimerization of CtBP and potentiate the therapeutic effect of cisplatin in a CtBP dimerization-dependent manner."	1.91	Metabolic modulation of CtBP dimeric status impacts the repression of DNA damage repair genes and the platinum sensitivity of ovarian cancer. ( Di, LJ; Hao, D; Li, J; Li, P; Liu, T; Lu, J; Su, M; Tai, L; Wang, L; Wang, Y; Zhao, Z, 2023)
"Metformin could inhibit the expression of CCNE1, which is associated with the anti-proliferative effect of tumor cells."	1.91	CCNE1 is a potential target of Metformin for tumor suppression of ovarian high-grade serous carcinoma. ( Chu, TY; Huang, HS; Liou, YL; Mei, J; Tian, H; Wang, J; Wu, N; Zhang, W, 2023)
"Ovarian cancer is the leading cause of death in gynecological malignancies worldwide."	1.72	Metformin inhibits the proliferation and invasion of ovarian cancer cells by suppressing tripartite motif-containing 37-induced tumor necrosis factor receptor-associated factor 2 ubiquitination. ( Sun, H; Zhang, H; Zheng, Y, 2022)
"Metformin was the most used medication (n = 3232) and consistently demonstrated survival benefit compared with tier 2 and 3 medications, across all methods."	1.72	Metformin and survival: Is there benefit in a cohort limited to diabetic women with endometrial, breast, or ovarian cancer? ( Buckanovich, RJ; Coffman, L; Edwards, RP; Lemon, LS; Modugno, F; Orr, B; Taylor, S, 2022)
"The role of IL‑8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated."	1.62	Interleukin‑8 released by cancer‑associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells. ( Ferraresi, A; Isidoro, C; Jamjuntra, P; Therasakvichya, S; Thongchot, S; Thuwajit, C; Thuwajit, P; Warnnissorn, M, 2021)
"Ovarian cancer is the most lethal gynecological malignancy in women."	1.62	Metformin Affects the Transcriptomic Profile of Chicken Ovarian Cancer Cells. ( Albert, I; Gopalan, L; Praul, CA; Ramachandran, R; Sebastian, A, 2021)
"We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin."	1.56	Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer. ( Chou, PC; Huang, CF; Lee, MH; Lin, JH; Sung, PL; Wen, KC; Wu, ATH; Yeung, SJ, 2020)
"Ovarian cancer is a gynecological cancer that has the highest mortality rate and is often resistant to conventional treatments."	1.56	Combination of metformin and RG7388 enhances inhibition of growth and induction of apoptosis of ovarian cancer cells through the PI3K/AKT/mTOR pathway. ( Cui, Y; Rong, F; Zhou, J, 2020)
"Metformin has long been an attractive therapeutic option for EwS, but hypoxia limits its efficacy."	1.56	Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways. ( Cheng, H; Lau, CC; Nan, X; Qiu, B; Sheng, J; Wang, J; Wong, STC; Yin, Z; Yustein, JT; Zhao, H, 2020)
"The role of phospholipid signaling in ovarian cancer is poorly understood."	1.51	SPHK1 Is a Novel Target of Metformin in Ovarian Cancer. ( Chiang, CY; Chiyoda, T; Curtis, M; Hart, PC; Lastra, R; Lengyel, E; Liu, X; Locasale, JW; Loth, R; McGregor, SM; Romero, IL; Weigert, M, 2019)
"Metformin (MET) has received considerable attention in recent years for its anticancer potential activities."	1.51	Enhanced anti-proliferative and pro-apoptotic effects of metformin encapsulated PLGA-PEG nanoparticles on SKOV3 human ovarian carcinoma cells. ( Dadashpour, M; Faramarzi, L; Mahdavi, M; Sadeghzadeh, H; Zarghami, N, 2019)
" However, the effect of long term administration of low dose of metformin as an adjuvant to cisplatin and paclitaxel during acquirement of chemoresistant phenotype has not been investigated so far."	1.51	Long term treatment of metformin impedes development of chemoresistance by regulating cancer stem cell differentiation through taurine generation in ovarian cancer cells. ( Bishnu, A; Chaudhury, K; Choudhury, P; Ghosh, N; Ray, P; Sakpal, A, 2019)
"Metformin has been shown to act in synergy with certain anti-cancer agents, overcoming chemoresistance in various types of tumors."	1.48	Chemosensitizing effects of metformin on cisplatin- and paclitaxel-resistant ovarian cancer cell lines. ( Dos Santos Guimarães, I; Dos Santos, DZ; Gimba, ERP; Ladislau-Magescky, T; Rangel, LBA; Silva, IV; Sternberg, C; Tessarollo, NG, 2018)
"We assessed the prognosis of ovarian cancer in women with type 2 diabetes treated with metformin, other forms of antidiabetic medication, or statins."	1.48	Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study. ( Arffman, M; Arima, R; Hautakoski, A; Hinkula, M; Ilanne-Parikka, P; Kangaskokko, J; Läärä, E; Marttila, M; Puistola, U; Sund, R; Urpilainen, E, 2018)
"BACKGROUND Ovarian cancer is considered one of the lethal cancers responsible for high mortality and morbidity across the world."	1.48	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. ( Chen, H; Du, J; Wang, B; Yang, L; Zhang, F, 2018)
"Metformin was demonstrated to evoke metabolic stress and induce cancer cell death."	1.48	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3). ( Bryś, M; Forma, E; Marczak, A; Rogalska, A; Śliwińska, A, 2018)
"High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy."	1.48	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells. ( Bukowska, B; Marczak, A; Rogalska, A, 2018)
"In all, 303 women were diagnosed with ovarian cancer during the follow up."	1.48	The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study. ( Arffman, M; Arima, R; Hautakoski, A; Hinkula, M; Ilanne-Parikka, P; Kangaskokko, J; Läärä, E; Marttila, M; Puistola, U; Sund, R; Urpilainen, E, 2018)
"Ovarian cancer is a devastating disease due to its high incidence of relapse and chemoresistance."	1.48	Metformin Suppresses Tumor Progression by Inactivating Stromal Fibroblasts in Ovarian Cancer. ( Chen, G; Gao, Q; Jin, P; Li, X; Long, S; Ma, D; Sun, C; Wang, Y; Wei, X; Xu, S; Yang, X; Yang, Z; Zhang, T, 2018)
"However, the role of complex I in ovarian cancer is largely unknown."	1.48	SIRT3 aggravates metformin-induced energy stress and apoptosis in ovarian cancer cells. ( Gao, WN; Lu, SY; Su, J; Sun, LK; Wu, Y; Xue, YN; Yan, XY; Yu, HM; Zhang, JJ; Zhang, LC, 2018)
"Metformin treatment significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK), and reduced histone H3 lysine 27 trimethylation (H3K27me3) and polycomb repressor complex 2 (PRC2) levels."	1.48	Metformin inhibits ovarian cancer via decreasing H3K27 trimethylation. ( Cai, J; Guo, J; Huang, Z; Liu, T; Tang, G; Wang, Z; Yu, L; Zhu, Y, 2018)
"Metformin use was not associated with overall survival in the entire cohort (HR 0."	1.46	A SEER-Medicare analysis of the impact of metformin on overall survival in ovarian cancer. ( Balkrishnan, R; Camacho, F; Cantrell, LA; Garcia, C; Yao, A, 2017)
"Treatment of metformin on SKOV-3 and A2780 cells of human ovarian cancer showed significant apoptosis."	1.46	Inhibitory effect and mechanism of metformin on human ovarian cancer cells SKOV-3 and A2780. ( Bian, XH; Huang, Y; Huo, J; Miao, ZC; Song, LH, 2017)
"Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed."	1.46	Inhibition of the IGF signaling pathway reverses cisplatin resistance in ovarian cancer cells. ( Du, J; Li, X; Ren, F; Shi, HR; Wang, JL; Wu, QH; Zhang, RT, 2017)
"Evidence indicates that type 2 diabetes may stimulate the initiation and progression of several types of cancer."	1.46	Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer: A retrospective study. ( Jia, YM; Lei, KJ; Liu, JP; Wang, SB, 2017)
"Low-grade serous ovarian cancer (LGSOC) constitutes 5-8% of epithelial ovarian cancers and is refractory to chemotherapy."	1.46	Synergistic effect of MEK inhibitor and metformin combination in low grade serous ovarian cancer. ( Allo, G; Carey, MS; Chhina, J; Dai, J; Giri, S; Llaurado, M; Mert, I; Munkarah, AR; Rattan, R; Seward, S, 2017)
"Metformin treatment in the presence of inhibitors of PERK and autophagy, however, had no cytotoxic effects on OSE or PBMC."	1.43	Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2α) pathway protect ovarian cancer cells from metformin-induced apoptosis. ( Gwak, H; Kim, B; Moon, HS; Song, YS; Suh, DH, 2016)
"BRCA mutated ovarian cancers show increased responsiveness to PARP inhibitors."	1.43	Preclinical evaluation of olaparib and metformin combination in BRCA1 wildtype ovarian cancer. ( Al-Wahab, Z; Ali-Fehmi, R; Buekers, T; Chhina, J; Dar, S; Hijaz, M; Mert, I; Munkarah, AR; Rattan, R; Taylor, M, 2016)
"The effect of metformin in ovarian cancer was tested in vitro and with 2 different mouse models."	1.42	Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models. ( Bradaric, M; Johnson, A; Lee, W; Lengyel, E; Litchfield, LM; Mitra, AK; Mukherjee, A; Nieman, KM; Romero, IL; Zhang, Y, 2015)
"Metformin was treated as a time-dependent variable; and of these patients, 286,106 were never-users, and 193,369 were ever-users."	1.42	Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus. ( Tseng, CH, 2015)
"Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice."	1.42	Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction. ( Al-Wahab, Z; Ali-Fehmi, R; Chhina, J; Giri, S; Hijaz, M; Mert, I; Morris, RT; Munkarah, AR; Rattan, R; Tebbe, C, 2015)
"Metformin treatment of ovarian cancer cells decreased both mRNA and protein levels of Axl and Tyro3 in a dose‑dependent manner."	1.42	Metformin targets Axl and Tyro3 receptor tyrosine kinases to inhibit cell proliferation and overcome chemoresistance in ovarian cancer cells. ( Kim, NY; Lee, C; Lee, HY, 2015)
"In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs."	1.42	Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer. ( Eckert, MA; Johnson, A; Lengyel, E; Litchfield, LM; Mills, KA; Mukherjee, A; Pan, S; Romero, IL; Shridhar, V, 2015)
"When metformin was combined with carboplatin or paclitaxel, an increased apoptotic activity was observed, implicating a chemo-adjuvant potential."	1.42	Metformin and epithelial ovarian cancer therapeutics. ( Kumar, L; Patel, S; Singh, N, 2015)
"Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins."	1.42	Evaluation of Effects of Metformin in Primary Ovarian Cancer Cells. ( Kumar, L; Patel, S; Singh, N, 2015)
"Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo."	1.42	Inhibitory effects of metformin at low concentration on epithelial-mesenchymal transition of CD44(+)CD117(+) ovarian cancer stem cells. ( Hou, D; Li, C; Li, W; Wang, H; Xiao, G; Zhang, P; Zhang, R, 2015)
"The aim of the present study was to determine the effects of metformin, combined with a p38 mitogen‑activated protein kinase (MAPK) inhibitor, on the sensitivity of cisplatin‑resistant ovarian cancer to cisplatin."	1.40	Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatin‑resistant ovarian cancer. ( Guo, H; Ji, M; Peng, Z; Shi, H; Shi, M; Xie, Y, 2014)
"This association is less clear in epithelial ovarian cancer (EOC)."	1.40	Diabetes mellitus and ovarian cancer: more complex than just increasing risk. ( Daily, LB; Erickson, BK; Fauci, JM; Haygood, CW; Leath, CA; Martin, JY; Matin, T; McGwin, G; Pasko, D; Shah, MM, 2014)
"Omental adipocytes promote ovarian cancer by secretion of adipokines, cytokines and growth factors, and acting as fuel depots."	1.40	Metformin limits the adipocyte tumor-promoting effect on ovarian cancer. ( Chhina, J; Dar, SA; Giri, S; Munkarah, AR; Rattan, R; Sarigiannis, K; Tebbe, C, 2014)
"Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin."	1.39	Metformin, at concentrations corresponding to the treatment of diabetes, potentiates the cytotoxic effects of carboplatin in cultures of ovarian cancer cells. ( Alonso, C; Barra, A; Barriga, MI; Brañes, J; Bravo, E; Bravo, ML; Bustamente, E; Cuello, MA; Erices, R; Garrido, M; Gonzalez, P; Ibañez, C; Kato, S; Oliva, B; Owen, GI; Pizarro, J; Racordon, D, 2013)
"Metformin has antitumor activity in monotherapy and also synergistically with other anticancer agents."	1.39	[Metformin--new treatment strategies for gynecologic neoplasms]. ( Kiałka, M; Krzysiek, J; Milewicz, T; Mrozińska, S; Ociepka, A, 2013)
"To estimate whether metformin use by ovarian cancer patients with type II diabetes was associated with improved survival."	1.38	Relationship of type II diabetes and metformin use to ovarian cancer progression, survival, and chemosensitivity. ( Karrison, T; Lengyel, E; McCormick, A; McEwen, KA; Pannain, S; Park, S; Romero, IL; Yamada, SD, 2012)
"Diabetic patients with ovarian cancer who are taking metformin have better outcomes than those not taking metformin."	1.38	Metformin targets ovarian cancer stem cells in vitro and in vivo. ( Buckanovich, RJ; Cabrera, L; Ghannam, J; Johnston, CJ; Reynolds, RK; Shank, JJ; Yang, K, 2012)
"A2780 ovarian cancer cells were injected intraperitoneally in nude mice; A2780-induced tumors in nude mice, when treated with metformin in drinking water, resulted in a significant reduction of tumor growth, accompanied by inhibition of tumor cell proliferation (as assessed by immunohistochemical staining of Ki-67, Cyclin D1) as well as decreased live tumor size and mitotic cell count."	1.37	Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in vivo. ( Giri, S; Graham, RP; Maguire, JL; Rattan, R; Shridhar, V, 2011)
"We evaluated its effect on epithelial ovarian cancer cell lines."	1.35	In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. ( Beauchamp, MC; Bruchim, I; Gotlieb, WH; Gu, J; Lau, S; Pollak, MN; Saumet, J, 2008)

Research

Studies (99)

Authors

Clinical Trials (6)

Trial Overview

Trial Outcomes

Overall Survival

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (1.01)	29.6817
2010's	73 (73.74)	24.3611
2020's	25 (25.25)	2.80

Authors	Studies
Gralewska, P	1
Gajek, A	1
Marczak, A	4
Rogalska, A	4
Gopalan, L	1
Sebastian, A	1
Praul, CA	1
Albert, I	1
Ramachandran, R	1
Lemon, LS	1
Orr, B	1
Modugno, F	2
Buckanovich, RJ	4
Coffman, L	1
Edwards, RP	1
Taylor, S	1
Goenka, L	1
Dubashi, B	1
Selvarajan, S	1
Ganesan, P	1
Guo, M	1
Shang, X	1
Guo, D	1
Zheng, Y	3
Zhang, H	2
Sun, H	3
Mei, J	1
Tian, H	1
Huang, HS	1
Wu, N	1
Liou, YL	1
Chu, TY	1
Wang, J	3
Zhang, W	1
Tossetta, G	1
Li, J	1
Wang, Y	5
Wang, L	2
Hao, D	1
Li, P	1
Su, M	1
Zhao, Z	1
Liu, T	2
Tai, L	1
Lu, J	1
Di, LJ	1
McCloskey, CW	1
Cook, DP	1
Kelly, BS	1
Azzi, F	1
Allen, CH	1
Forsyth, A	1
Upham, J	1
Rayner, KJ	1
Gray, DA	1
Boyd, RW	1
Murugkar, S	1
Lo, B	1
Trudel, D	1
Senterman, MK	1
Vanderhyden, BC	1
Zhu, J	2
Liu, Y	2
Nan, X	1
Cheng, H	1
Yin, Z	1
Sheng, J	1
Qiu, B	1
Lau, CC	1
Yustein, JT	1
Zhao, H	1
Wong, STC	1
Hart, PC	3
Kenny, HA	1
Grassl, N	1
Watters, KM	1
Litchfield, LM	4
Coscia, F	1
Blaženović, I	1
Ploetzky, L	1
Fiehn, O	1
Mann, M	1
Lengyel, E	6
Romero, IL	6
Broekman, KE	1
Hof, MAJ	1
Touw, DJ	1
Gietema, JA	1
Nijman, HW	1
Lefrandt, JD	1
Reyners, AKL	1
Jalving, M	1
Cole, AJ	1
Fayomi, AP	1
Anyaeche, VI	1
Bai, S	1
Majidi, A	1
Na, R	1
Dixon-Suen, S	1
Jordan, SJ	1
Webb, PM	1
Brown, JR	1
Chan, DK	1
Shank, JJ	2
Griffith, KA	1
Fan, H	1
Szulawski, R	1
Yang, K	2
Reynolds, RK	2
Johnston, C	1
McLean, K	1
Uppal, S	1
Liu, JR	1
Cabrera, L	2
Taylor, SE	1
Orr, BC	1
Mehta, P	1
Bregenzer, M	1
Mehta, G	1
Shen, H	2
Coffman, LG	1
Yu, Z	1
Wang, B	2
Zhai, J	1
Wen, KC	1
Sung, PL	1
Wu, ATH	1
Chou, PC	1
Lin, JH	1
Huang, CF	1
Yeung, SJ	1
Lee, MH	1
Bukovsky, A	1
Cui, Y	1
Zhou, J	2
Rong, F	1
Nunes, M	1
Henriques Abreu, M	1
Bartosch, C	1
Ricardo, S	1
Dang, J	1
Gao, J	1
Ma, F	1
Luo, Y	1
Wang, D	1
Li, W	2
Li, L	1
Liu, X	5
Hu, D	1
Jin, Z	1
Tsogas, FK	1
Majerczyk, D	1
Thongchot, S	1
Jamjuntra, P	1
Therasakvichya, S	1
Warnnissorn, M	1
Ferraresi, A	1
Thuwajit, P	1
Isidoro, C	1
Thuwajit, C	1
Park, JY	1
Lim, MC	1
Baek, MH	1
Park, YH	1
Kim, S	1
Fu, YL	1
Zhang, QH	1
Wang, XW	1
He, H	1
Garcia, C	1
Yao, A	1
Camacho, F	1
Balkrishnan, R	1
Cantrell, LA	1
Mert, I	3
Chhina, J	4
Allo, G	1
Dai, J	1
Seward, S	1
Carey, MS	1
Llaurado, M	1
Giri, S	6
Rattan, R	7
Munkarah, AR	4
Markowska, A	2
Sajdak, S	2
Markowska, J	2
Huczyński, A	2
Wang, SB	1
Lei, KJ	1
Liu, JP	1
Jia, YM	1
Bukowska, B	1
Du, J	2
Shi, HR	1
Ren, F	1
Wang, JL	1
Wu, QH	1
Li, X	3
Zhang, RT	1
Urpilainen, E	2
Marttila, M	2
Hautakoski, A	2
Arffman, M	2
Sund, R	2
Ilanne-Parikka, P	2
Arima, R	2
Kangaskokko, J	2
Puistola, U	2
Läärä, E	2
Hinkula, M	2
Xu, S	1
Yang, Z	2
Jin, P	1
Yang, X	1
Wei, X	1
Long, S	1
Zhang, T	2
Chen, G	1
Sun, C	1
Ma, D	1
Gao, Q	1
Wu, Y	2
Gao, WN	1
Xue, YN	1
Zhang, LC	1
Zhang, JJ	1
Lu, SY	1
Yan, XY	1
Yu, HM	1
Su, J	1
Sun, LK	1
Tang, G	1
Guo, J	1
Zhu, Y	1
Huang, Z	1
Cai, J	1
Yu, L	1
Wang, Z	1
Dos Santos Guimarães, I	1
Ladislau-Magescky, T	1
Tessarollo, NG	1
Dos Santos, DZ	1
Gimba, ERP	1
Sternberg, C	1
Silva, IV	1
Rangel, LBA	1
Rehlis, S	1
Zhang, F	1
Chen, H	1
Yang, L	2
Forma, E	2
Bryś, M	2
Śliwińska, A	1
Kobayashi, Y	1
Banno, K	1
Kunitomi, H	1
Tominaga, E	1
Aoki, D	1
Bishnu, A	1
Sakpal, A	1
Ghosh, N	1
Choudhury, P	1
Chaudhury, K	1
Ray, P	1
Shi, J	1
Liu, B	1
Wang, H	2
Chiyoda, T	1
Weigert, M	1
Curtis, M	1
Chiang, CY	1
Loth, R	1
Lastra, R	1
McGregor, SM	1
Locasale, JW	2
Ma, L	1
Wei, J	1
Wan, J	1
Wang, W	1
Yuan, Y	1
Ming, L	1
Lee, J	1
An, S	1
Jung, JH	1
Kim, K	1
Kim, JY	1
An, IS	1
Bae, S	1
Faramarzi, L	1
Dadashpour, M	1
Sadeghzadeh, H	1
Mahdavi, M	1
Zarghami, N	1
Lu, MZ	1
Li, DY	1
Wang, XF	1
Yan, P	1
Bi, Y	1
Zhang, ZJ	2
Mormile, R	1
Erices, R	2
Bravo, ML	2
Gonzalez, P	2
Oliva, B	2
Racordon, D	1
Garrido, M	1
Ibañez, C	2
Kato, S	2
Brañes, J	2
Pizarro, J	1
Barriga, MI	1
Barra, A	1
Bravo, E	2
Alonso, C	2
Bustamente, E	1
Cuello, MA	2
Owen, GI	2
Milewicz, T	1
Kiałka, M	1
Mrozińska, S	1
Ociepka, A	1
Krzysiek, J	1
Holzgreve, H	1
Dilokthornsakul, P	1
Chaiyakunapruk, N	1
Termrungruanglert, W	1
Pratoomsoot, C	1
Saokaew, S	1
Sruamsiri, R	1
Li, S	2
Tebbe, C	2
Dar, SA	1
Sarigiannis, K	1
Kim, TH	1
Suh, DH	2
Kim, MK	1
Song, YS	3
Hu, T	1
Chung, YM	1
Guan, M	1
Ma, M	1
Ma, J	1
Berek, JS	1
Hu, MC	1
Yan, L	1
Gao, Y	1
Ghazal, S	1
Lu, L	1
Bellone, S	1
Yang, Y	1
Liu, N	1
Zhao, X	1
Santin, AD	1
Taylor, H	1
Huang, Y	3
Wójcik-Krowiranda, K	1
Ciesielski, P	1
Bieńkiewicz, A	1
Krzeslak, A	1
Xie, Y	1
Peng, Z	1
Shi, M	1
Ji, M	1
Guo, H	1
Shi, H	1
Stine, JE	1
Bae-Jump, V	1
Shah, MM	1
Erickson, BK	1
Matin, T	1
McGwin, G	1
Martin, JY	1
Daily, LB	1
Pasko, D	1
Haygood, CW	1
Fauci, JM	1
Leath, CA	1
Mitra, AK	1
Nieman, KM	1
Mukherjee, A	2
Zhang, Y	2
Johnson, A	2
Bradaric, M	1
Lee, W	1
Moon, HS	1
Kim, B	1
Gwak, H	2
Tseng, CH	1
Al-Wahab, Z	2
Hijaz, M	2
Morris, RT	1
Ali-Fehmi, R	2
Kim, NY	1
Lee, HY	1
Lee, C	1
Eckert, MA	1
Mills, KA	1
Pan, S	1
Shridhar, V	4
Patel, S	2
Kumar, L	2
Singh, N	2
Duda, K	1
Cholewa, H	1
Łabuzek, K	1
Boratyn-Nowicka, A	1
Okopień, B	1
Zhang, R	1
Zhang, P	1
Hou, D	1
Xiao, G	1
Li, C	2
Kim, Y	1
An, H	1
Dhanasekaran, DN	1
Matassa, DS	1
Amoroso, MR	1
Lu, H	1
Avolio, R	1
Arzeni, D	1
Procaccini, C	1
Faicchia, D	1
Maddalena, F	1
Simeon, V	1
Agliarulo, I	1
Zanini, E	1
Mazzoccoli, C	1
Recchi, C	1
Stronach, E	1
Marone, G	1
Gabra, H	1
Matarese, G	1
Landriscina, M	1
Esposito, F	1
Desir, S	1
Dickson, EL	1
Vogel, RI	1
Thayanithy, V	1
Wong, P	1
Teoh, D	1
Geller, MA	1
Steer, CJ	1
Subramanian, S	1
Lou, E	1
Taylor, M	1
Dar, S	1
Buekers, T	1
Gadducci, A	1
Biglia, N	1
Tana, R	1
Cosio, S	1
Gallo, M	1
Li, B	1
Ni, Z	1
Zeng, Y	1
Yan, X	1
He, J	1
Lyu, X	1
He, F	1
Galdieri, L	1
Gatla, H	1
Vancurova, I	1
Vancura, A	1
Cubillos, S	1
Aravena, R	1
Santoro, F	1
Marquez, M	1
Orellana, R	1
Ramírez, C	1
Fuenzalida, P	1
García, K	1
Arab, C	1
Torres, VA	1
Godoy, AS	1
Pereira, J	1
Bustos, G	1
Cardenas, JC	1
Huo, J	1
Bian, XH	1
Miao, ZC	1
Song, LH	1
Hartmann, LC	1
Yasmeen, A	2
Beauchamp, MC	3
Piura, E	1
Segal, E	1
Pollak, M	2
Gotlieb, WH	3
Graham, RP	1
Maguire, JL	1
Bodmer, M	1
Becker, C	1
Meier, C	1
Jick, SS	1
Meier, CR	1
Segal, ED	1
Rosenblatt, J	1
Liu, VW	1
Chan, DW	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
The Possible Effect of Itraconazole as add-on Therapy to Paclitaxel and Carboplatin on the Treatment Outcome in Patients With Advanced Ovarian Cancer[NCT05591560]		66 participants (Anticipated)	Interventional	2022-10-31	Not yet recruiting
Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population[NCT05317806]	Phase 4	15 participants (Anticipated)	Interventional	2022-10-10	Active, not recruiting
Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients[NCT05298670]	Phase 2	80 participants (Anticipated)	Interventional	2022-02-01	Recruiting
A Phase II Evaluation of Metformin, Targeting Cancer Stem Cells for the Prevention of Relapse in Patients With Stage IIC/III/IV Ovarian, Fallopian Tube, and Primary Peritoneal Cancer[NCT01579812]	Phase 2	90 participants (Actual)	Interventional	2011-10-31	Completed
Endometrial Cancer Recurrence in Patients Taking Metformin[NCT05192850]		100 participants (Anticipated)	Observational	2021-12-27	Active, not recruiting
Metformin and Neo-adjuvant Temozolomide and Hypofractionated Accelerated Limited-margin Radiotherapy Followed by Adjuvant Temozolomide in Patients With Glioblastoma Multiforme (M-HARTT STUDY)[NCT02780024]	Phase 2	50 participants (Anticipated)	Interventional	2015-03-31	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Determine the median overall survival time for all patients who complete treatment as well as for patients presenting with stage IIc/ III and stage IV ovarian cancer. (NCT01579812)
Timeframe: Up to 3 Years

Recurrence-Free Survival

Intervention	months (Median)
Metformin - All Patients Analyzed	43
Metformin - Patients Stage IIc/ III Ovarian Cancer	52
Metformin - Patients With Stage IV Ovarian Cancer	36

"Determine the percentage of patients alive without recurrence at 18 months. Investigators will also determine recurrence free survival when patients with persistent disease are excluded.~Definition of progression or recurrence and survival will be defined as increasing clinical, radiological or histological evidence of disease since study entry or two serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN) performed at least one week apart, regardless of CT scan results.~Recurrence-Free Interval will be defined as date from start of chemotherapy to the date of first clinical, biochemical, or radiological evidence of progression or death due to any cause." (NCT01579812)
Timeframe: 18 months

Intervention	percentage of patients (Number)
Metformin - All Patients Analyzed	58.1
Metformin - Patients With Persistent Disease Excluded	55.6

metformin and Ovarian Neoplasms