The Pathway from Diabetes and Obesity to Cancer, on the Route to Targeted Therapy

On the Route to Targeted Therapy

Emily J. Gallagher, MBBCh, MRCPI; Yvonne Fierz, MD; Rosalyn D. Ferguson, PhD; Derek LeRoith, MD, PhD

Disclosures

Endocr Pract. 2010;16(5):864-873. 

In This Article

Abstract and Introduction

Abstract

Objective: 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.
Methods: 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.
Results: Epidemiologic studies have reported that diabetes and obesity are linked to an increased risk of certain cancers in association with higher levels of insulin, C-peptide, and insulinlike growth factor 1. Animal models have demonstrated that increased insulin, insulinlike growth factor 1, and insulinlike growth factor 2 signaling can enhance tumor growth, while inhibiting this signaling can reduce tumorigenesis. Therapies that target insulin and insulinlike growth factor 1 signaling pathways have been developed and are currently in clinical trials to treat cancer.
Conclusions: 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.

Introduction

Observational studies have shown an association between diabetes, obesity, and cancer. It is hypothesized that insulin resistance with hyperinsulinemia and increased insulin and insulinlike growth factor (IGF) signaling account, to some extent, for the relationship between these conditions. 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. We review the epidemiologic studies that describe the relationship between diabetes, obesity, and cancer; animal studies that have helped to decipher the mechanisms of cancer development; and some of the therapeutic targets undergoing investigation.

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