Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2441
Peer-review started: September 29, 2015
First decision: November 27, 2015
Revised: December 17, 2015
Accepted: January 9, 2016
Article in press: January 11, 2016
Published online: February 28, 2016
Processing time: 150 Days and 3.1 Hours
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.
Core tip: Pancreatic cancer has a dismal prognosis with an overall five years survival less than 5%. Obesity and diabetes are risk factors of pancreatic ductal adenocarcinoma (PDAC) increasing the likelihood of its development. Agonists of one specific nuclear receptor transcription factor, the peroxisome proliferator-activated receptor γ (PPARγ), are currently used or evaluated for the treatment of these diseases. PPARγ is a well-known protein implicated in the regulation of metabolism, inflammation, and differentiation; standing at the cross-road of these diseases it may be a key factor linking PDAC to diabetes and obesity, a master regulator whose modulation could be the key for PDAC treatment.