Kinase Regulating Pancreatic Cancer Resistance to Chemotherapeutics

"Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of cancer known to date with the lowest overall 5-year survival rate. PDAC is extremely resistant to conventional chemotherapies, and there is a desperate need to identify new targets for molecular therapeutics. The resistance to common chemotherapeutics in pancreatic cancer and PDAC cell lines is tightly linked to NF-kappaB activity. NF-kappaB is an inducible transcription factor which, dependent on the stimulus, is regulated by a variety of kinase-regulated signaling cascades. Our project is designed to identify kinases that regulate resistance of pancreatic cancer cells to chemotherapeutic agents. Such kinases may serve as potential drug targets for pancreatic cancer therapy. We will employ a global approach to uncover these key enzymes and test if some of them could serve as targets for novel therapeutics to decrease the resistance of pancreatic cancer to chemotherapeutic agents. Once these kinases are identified we will screen compound libraries for specific inhibitors and test if they affect PDAC resistance to chemotherapeutics. The AACR-Pancreatic Cancer Action Network Career Development Award for Pancreatic Cancer research will allow us to identify kinases that may serve as potential drug targets for pancreatic cancer therapy and contribute to develop a strategy to re-sensitize pancreatic tumor cells to conventional chemotherapeutic agents."