GLT-1 Modulators for the Pancreatic ductal adenocarcinoma: Pancreatic ductal adenocarcinoma is an aggressive and deadly disease that is characterized by invasive, metastatic progression and profound resistance to conventional therapeutics. 43,000 new cases and 36,000 deaths were attributed to pancreatic cancer in 2010, and it is the fourth most common cause of cancer death in the US. The disease is asymptomatic in the early and mid stages, leading to limited early detection. Limited detection in early stages coupled with lack of effective chemotherapeutics contributes to the low 1 and 5 year survival rate of 25% and 6% respectively.
One of the central players in tumor growth and progression is Glutamate (Glu) and the corresponding transporter, Glutamate Transporter 1 (GLT-1). It has recently been demonstrated that GLT-1 is functionally expressed in pancreatic b-cells, and prevents Glu induced cytotoxicity in pancreatic cancer cells. Also, Glu concentration plays a key role in pancreatic cancer cell invasion and migration, suggesting that modulation of Glu levels would have a positive impact on the progression of pancreatic cancer. The overall objective of this project is to discover novel small molecule modulators of GLT-1 mediated glutamate transport to develop an improved understanding of the role of GLT-1 and glutamate transport in pancreatic cancer.