Dataset Information

The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?

ABSTRACT: The role of metformin in ovarian cancer (OC) remains a topic of research and open discussion. Because OC has a high mortality rate for various reasons, finding a solution is vital. Although metformin has demonstrated a high level of evidence in preventing and increasing survival in other cancers, its role in OC is still not proven. This review highlights the function of metformin as an antineoplastic agent in OC and its effect on overall survival, progress-free survival, and recurrence-free survival. We conducted a literature search in the PubMed database using the medical subject heading keywords, ovarian neoplasm and metformin. The search yielded 94 articles, of which 86 remained after including only English language articles. Finally, 50 articles published between 1997 and 2020 were reviewed. We recommend more randomized controlled trials in the future to determine the safety and efficacy of metformin in OC.

SUBMITTER: Ahmed MF

PROVIDER: S-EPMC7861091 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?

Ahmed Maimuna F MF Kanaan Ghid G Mostafa Jihan A JA

Cureus 20210203 2

The role of metformin in ovarian cancer (OC) remains a topic of research and open discussion. Because OC has a high mortality rate for various reasons, finding a solution is vital. Although metformin has demonstrated a high level of evidence in preventing and increasing survival in other cancers, its role in OC is still not proven. This review highlights the function of metformin as an antineoplastic agent in OC and its effect on overall survival, progress-free survival, and recurrence-free surv ...[more]

PMID: 33564559

Similar Datasets

Project description:BackgroundThe objective of this case-control study was to identify any association of metformin intake with the survival of patients with ovarian cancer.MethodsIn this retrospective case-control study, women with ovarian cancer who received metformin (cases) were compared with women with ovarian cancer who did not receive metformin (controls). A 2-layered analysis was conducted. In preliminary analysis, all cases (the OC cohort) were compared with controls at a 1:2 ratio. Subsequently, in definitive analysis, only patients who had epithelial ovarian cancer (the EOC cohort) were compared with controls at a 1:3 ratio. In the EOC cohort, cases were matched with controls for age (±5 years), International Federation of Gynecology and Obstetrics stage, and residual disease. Prognostic variables and disease specific survival were compared using chi-square tests, the Kaplan-Meier (log-rank) method, and Cox proportional hazards analysis.ResultsIn a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5-year disease-specific survival for cases vs controls, 73% vs 44%; P = .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5-year disease-specific survival for cases vs controls, 67% vs 47%; P = .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8; P = .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.ConclusionsThe results of this study indicated an association of metformin intake with survival in patients with ovarian cancer. The receipt of metformin was associated with better survival, and the authors concluded that metformin is worthy of clinical trials in ovarian cancer.

Project description:The role of phospholipid signaling in ovarian cancer is poorly understood. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingosine that has been associated with tumor progression through enhanced cell proliferation and motility. Similarly, sphingosine kinases (SPHK), which catalyze the formation of S1P and thus regulate the sphingolipid rheostat, have been reported to promote tumor growth in a variety of cancers. The findings reported here show that exogenous S1P or overexpression of SPHK1 increased proliferation, migration, invasion, and stem-like phenotypes in ovarian cancer cell lines. Likewise, overexpression of SPHK1 markedly enhanced tumor growth in a xenograft model of ovarian cancer, which was associated with elevation of key markers of proliferation and stemness. The diabetes drug, metformin, has been shown to have anticancer effects. Here, we found that ovarian cancer patients taking metformin had significantly reduced serum S1P levels, a finding that was recapitulated when ovarian cancer cells were treated with metformin and analyzed by lipidomics. These findings suggested that in cancer the sphingolipid rheostat may be a novel metabolic target of metformin. In support of this, metformin blocked hypoxia-induced SPHK1, which was associated with inhibited nuclear translocation and transcriptional activity of hypoxia-inducible factors (HIF1α and HIF2α). Further, ovarian cancer cells with high SPHK1 were found to be highly sensitive to the cytotoxic effects of metformin, whereas ovarian cancer cells with low SPHK1 were resistant. Together, the findings reported here show that hypoxia-induced SPHK1 expression and downstream S1P signaling promote ovarian cancer progression and that tumors with high expression of SPHK1 or S1P levels might have increased sensitivity to the cytotoxic effects of metformin. IMPLICATIONS: Metformin targets sphingolipid metabolism through inhibiting SPHK1, thereby impeding ovarian cancer cell migration, proliferation, and self-renewal.

Dataset Information

The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?

Publications

The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets