Project Title: Role of phosphoinositide 3-kinase class IB
in human pancreatic cancer
Research Aims: Pancreatic cancer has one of the poorest prognoses among all cancers, therefore definition of the intracellular mechanism leading to its development and progression may define novel therapeutic strategies. A number of genetic and epigenetic disturbances have been identified in human pancreatic cancer such as mutations in K-ras oncogene. One of the key downstream targets of the Ras family is phosphoinositide 3-kinase (PI3K), the enzyme responsible for generation of 3-phosphorylated phosphoinositides and activation of the protein kinase Akt. Hyperactivation of Akt has been observed in pancreatic cancer and represents a biological indicator of the aggressiveness of the disease. The goal of this study is to define the role of a specific PI3K isoform p110 gamma in pancreatic cancer. Our hypothesis is that p110gamma overexpression is a frequent and early event in pancreatic cancer progression and could therefore potentially influence important pathophysiological aspects of pancreatic ductal adenocarcinoma, such as apoptosis and chemoresistance.
In this project we plan to investigate the specific role of p110gamma in pancreatic cancer and characterize the p110-dependent signalling pathways. Pancreatic cancer is one of the most lethal human cancers and represents a challenging problem in modern medicine. Conventional anticancer therapies have little impact on this aggressive neoplasm. In this respect our identification of an emerging novel signal transduction pathway in pancreatic cancer represents a potential avenue that will eventually lead to novel therapeutic strategies.