How far along are we in revealing the connection between metformin and colorectal cancer?

Abstract

Colorectal cancer (CRC) is among the most prevalent cancers worldwide, and its prevention and reduction of incidence is imperative. The presence of diabetes has been associated with a 30% increased risk of CRC, likely through the mechanism of hyperinsulinemia, which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways, inflammation, or adipokines, inducing cancer cell proliferation and cancer spread. Metformin, the first-line agent in treating type 2 diabetes, has a chemopreventive role in CRC development. Additionally, preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon cancer. Although preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy, the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive, and randomized controlled trials are still lacking.

Deep Phosphoproteomic Elucidation of Metformin-Signaling in Heterogenous Colorectal Cancer Cells

“…Type II diabetes patients have been shown to suffer from increased risk of developing CRC (Berkovic et al ., 2021). Mounting evidence suggests that the first line type II diabetes drug, metformin, could be beneficial in preventing the CRC development and improving the cancer prognosis (Berkovic et al ., 2021).…”

“…Type II diabetes patients have been shown to suffer from increased risk of developing CRC (Berkovic et al ., 2021). Mounting evidence suggests that the first line type II diabetes drug, metformin, could be beneficial in preventing the CRC development and improving the cancer prognosis (Berkovic et al ., 2021). The MoA of metformin is pleiotropic, affecting both whole organism and cellular level (Pernicova and Korbonits, 2014; Rena et al ., 2017), but not yet completely understood.…”

“…Furthermore, metformin can affect cellular signaling in an AMPK-independent manner (Stein et al, 2019). Therefore, the MoA underlying metformin’s gastrointestinal anti-cancer properties seems pleiotropic and remains largely mysterious (Berkovic et al ., 2021; Kulkarni et al ., 2020; Pernicova and Korbonits, 2014; Rena et al, 2017).…”

Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing

“…Metformin, an oral anti-diabetic medication used for type 2 diabetes mellitus, is a biguanide drug that increases insulin sensitivity, decreases intestinal absorption of glucose, and decreases its production by the liver [100]. Previous studies have shown a protective effect of metformin in CRC risk and prognosis [101,102]. The current understanding is that metformin inhibits the mammalian target of rapamycin (mTOR) pathway which plays a central role in CRC cell growth and proliferation [49].…”

New Diabetic Medication Sodium-Glucose Cotransporter-2 Inhibitors Can Induce Euglycemic Ketoacidosis and Mimic Surgical Diseases: A Case Report and Review of Literature

“…Diabetes mellitus (DM) itself is a well-established risk factor and/or comorbidity for several pathologies seen in surgical wards, such as gastrointestinal malignancy, abdominal, and/or peripheral artery disease, likely with amputation and obesity with bariatric surgery ( 6 – 8 ).…”