Novel drug targets based on association between inflammation and pancreatic ductal adenocarcinoma.

We read with great interest the editorial published by Uomo et al. in the 2010 May issue of JOP. J Pancreas (Online) titled: “Inflammation and Pancreatic Ductal Adenocarcinoma: A Potential Scenario for Novel Drug Targets” [1]. There is a growing amount of evidence that inflammation plays a contributory role in the pathogenesis of cancer, including pancreatic carcinogenesis. Inflammatory states are characterized by the formation of reactive oxygen species and the induction of cell cycling for tissue growth and repair [1, 2, 3]. The initiation, promotion and expansion of tumors may be influenced by numerous components that also function in the inflammatory response. Recognized risk factors for pancreatic cancer include cigarette smoking, chronic/hereditary pancreatitis, obesity and type II diabetes. Each risk factor is linked by the fact that the inflammatory state significantly drives its pathology. We agree with the authors that multiple links between inflammation and pancreatic adenocarcinoma has led to development of novel targeted therapy which is under evaluation both in vivo and in vitro studies to fight against pancreatic adenocarcinoma. Pancreatic cancer is one of the leading causes of cancer mortality in the United States. Current therapy for pancreatic cancer involves surgery, chemotherapy, and radiation therapy; however, the 5-year survival rate remains less than 5%. Therefore, developments of novel agents, in particular based on the pathogenesis of pancreatic adenocarcinoma are urgently indicated. Nuclear Factor Kappa B (NF-kappa B) Activity Few agents affecting NF-kappa B activity includes: MG132, a proteasome inhibitor [4], thymoquinone [5], fisetin, a natural flavonoid [6], sulforaphane [7], lidamycin [8], curcumin [9] and PHY906, a Chinese botanical formulation [10]. Of note characterization of sonic hedgehog as a novel NF-kappa B target gene that promotes NF-kappa B-mediated apoptosis resistance and tumor growth is potentially very important [11].