Abstract PL05-02: Current therapies for diabetes - will they reduce cancer risk?

Type 2 diabetes has been associated with an increase in the incidence and mortality from many cancers. Understanding the mechanisms underlying Type 2 diabetes, has contributed to the discovery of the potential anti-cancer effects of diabetes treatments. Insulin resistance and hyperinsulinemia precede the development of hyperglycemia and Type 2 diabetes, and may be key factors contributing to the increased cancer risk. Other factors including hyperglycemia, steroid hormonal bioavailability (estrogen and testosterone), insulin-like growth factors, adipokines (leptin and adiponectin) and cytokines may also contribute to cancer progression in the setting of Type 2 diabetes. The main classes of pharmacological treatments for Type 2 diabetes include insulin-sensitizing therapies, insulin secretagogues, exogenous insulin and incretin based therapies. While some previous epidemiological studies suggested that exogenous insulin therapy may increase breast cancer mortality, recent human studies have not supported these findings. Our studies have shown that high doses of the insulin analogs currently in clinical use do not increase murine breast cancer growth or metastases in a mouse model of pre-diabetes. However, insulin-sensitizing therapies, including metformin and thiazolidinediones may have anti-cancer effects. One potential mechanism by which these agents may reduce tumor progression, is by improving the metabolic abnormalities associated with Type 2 diabetes; improving insulin sensitivity, decreasing endogenous insulin levels. Reducing insulin levels has been shown to reduce cancer growth in previous animal studies. In addition, or alternatively, these agents may act directly on the tumor cells. Metformin is taken up into cells by organic cation transporters, and is an activator of AMPK, which may reduce cell proliferation and tumor metastases. Thiazolidinediones are peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that also improve insulin resistance, and are effective in reducing the progression from pre-diabetes to Type 2 diabetes. While these agents demonstrated potential as anti-cancer agents in animal and in vitro studies, however, some epidemiological studies reported that these agents may increase bladder cancer risk, subsequent studies have not corroborated these findings. Therefore, Type 2 diabetes is associated with an increase in cancer incidence and mortality, understanding the mechanisms underlying this association has led to the potential use of anti-diabetic agents in the prevention and treatment of cancer.

Citation Format: Emily Jane Gallagher. Current therapies for diabetes - will they reduce cancer risk? [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL05-02.