The Pathway from Diabetes to Cancer

tumorigenesis.

The purpose of the study was to review the epidemiologic studies that describe the relationships among diabetes, obesity, and cancer; animal studies that have helped to decipher the mechanisms of cancer development; and some of the therapeutic targets undergoing investigation.

An electronic search was performed of Medline, Scopus, Google Scholar, and ClinicalTrials.gov to identify English-language articles and studies published from 1995 through 2010 relating to obesity, insulin, insulinlike growth factors, diabetes mellitus, and cancer.

From the results it was concluded that insulin, insulinlike growth factor 1, and insulinlike growth factor 2 signaling through the insulin receptor and the insulinlike growth factor 1 receptor can induce tumorigenesis, accounting to some extent for the link between diabetes, obesity, and cancer. Knowledge of these pathways has enhanced our understanding of tumor development and allowed for the discovery of novel cancer treatments. 

Evidence of an increased risk of cancer with diabetes and obesity from epidemiologic studies has led to great concern given the worldwide epidemic of obesity and diabetes. The intriguing data presented in this review suggest that this increased risk is related to higher levels of insulin and IGF-1. In vivo studies on animal models have been designed to tease apart the processes that explain these associations and to verify the credibility of the findings of epidemiologic studies. From these studies, we see that increased insulin, IGF-1, and IGF-2 signaling through the insulin receptor and IGF-1 receptor can in fact induce tumorigenesis by up-regulating the insulin receptor and IGF-1 receptor signaling pathways. In addition, disrupting these receptors or blocking their activity in animals prevents tumor growth and metastasis by inhibiting their downstream signaling. This knowledge has been exploited in the development of pharmacologic agents that target specific points in these pathways. Novel monoclonal antibodies against the IGF-1 receptor and TKI are auspicious targeted therapies that demonstrate great promise as cancer treatments. Furthermore, due to these epidemiologic and laboratory studies, metformin is undergoing a renaissance because of its potential as a cancer therapy along with its traditional role in treating diabetes.

Endocrine Practice. 2010;16(5):864-873