The pathway from diabetes and obesity to cancer, on the route to targeted therapy.
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.
Gallagher
Emily J
EJ
Division of Endocrinology, Diabetes, and Bone Diseases, The Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Fierz
Yvonne
Y
Ferguson
Rosalyn D
RD
LeRoith
Derek
D
D000818:Animals; D048909:Diabetes Complications / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology