Targeting Notch signaling in pancreatic cancer.
BACKGROUND
With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary. Because embryological signaling pathways are upregulated in pancreatic adenocarcinoma, they represent potential targets for future therapies.


METHODS
Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined.


RESULTS
Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog.


CONCLUSIONS
Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.
Ristorcelli
Elodie
E
INSERM UMR 911-CR02, Faculty of Medicine, 27 BL Jean Moulin, Marseille 13005, France.
Lombardo
Dominique
D
D006801:Humans; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D051880:Receptors, Notch