New strategies in pancreatic cancer: emerging epidemiologic and therapeutic concepts

Clin Cancer Res. 2010 Sep 1;16(17):4313-8. doi: 10.1158/1078-0432.CCR-09-1942. Epub 2010 Jul 20.


Pancreatic cancer (PC) is a highly lethal disease with complex etiology involving both environmental and genetic factors. Although cigarette smoking is known to explain 25% of cases, data from recent studies suggest that obesity and long-term type II diabetes are two major modifiable risk factors for PC. Furthermore, obesity and diabetes seem to affect the clinical outcome of patients with PC. Understanding the mechanistic effects of obesity and diabetes on the pancreas may identify new strategies for prevention or therapy. Experimental and epidemiologic evidence suggests that the antidiabetic drug metformin has protective antitumor activity in PC. In addition to insulin resistance and inflammation as mechanisms of carcinogenesis, obesity and diabetes are linked to impairments in endothelial function and coagulation status, which increase the risks of thrombosis and angiogenesis and, in turn, the risk of PC development and progression. The associations of the ABO blood group gene and NR5A2 gene variants with PC discovered by recent genome-wide association studies may link insulin resistance, inflammation, and thrombosis to pancreatic carcinogenesis. These exciting findings open new avenues for understanding the etiology of PC and provide opportunities for developing novel strategies for prevention and treatment of this disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Male
  • Metformin / therapeutic use*
  • Obesity / complications
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / etiology
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Risk Factors
  • Smoking / adverse effects
  • United States / epidemiology


  • Hypoglycemic Agents
  • NR5A2 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Metformin