Diabetes mellitus and metformin in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments.

New insight for metformin against bladder cancer

“…Furthermore, DM and obesity are considered as risk factors for bladder cancer. Metformin, a first-line oral anti-diabetic, has been demonstrated to prevent cancer and reduce cancer mortality among diabetic patients in observational studies [13]. Hence, in this review, I will shed light on the proposed mechanisms of anti-carcinogenic effects of metformin and correlation of these mechanisms with bladder cancer according to recent published literature (Fig.…”

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

“…The overall evidence supporting the potential beneficial effects of metformin in oncology has been reviewed previously and is summarized briefly below. The reader is also referred to other reviews for further details of its potential anticancer properties …”

“…The reader is also referred to other reviews for further details of its potential anticancer properties. [21][22][23][24][25][26] Metformin has been shown to inhibit proliferation of cancer cells in a number of in vitro studies. For example, glioblastoma is the most common and aggressive type of primary brain cancer, and the current standard therapy consists of maximal surgical resection within safe limits, followed by radiation therapy and chemotherapy with temozolomide.…”

Metformin and Its Implication in Cancer Therapy

“…One meta-analysis stated that metformin does not significantly reduce the risk of hepatocellular carcinoma. This meta-analysis excluded all the studies with timerelated biases [42,43].…”