Background: Metastases requires reorganisation of the actin cyto-skeleton3, a process dependent on proteins belonging to the Rho family GTPases; Rho, Rac and Cdc-41. Evidence supports theories that the p21-actiavted kinase family (PAK1-6)may play a key role in cell migration, cell survival and regulation key-hallmarks of the development and progression of cancer(Ca). Our preliminary published data suggest that PAK1-6 may be active and that PAK4 may be required for invasion. However, other isoforms has not been investigated. This group recently demonstrated somatic PAK4 mutation activity and PAK5 mutations have been identified in pancreatic Ca. Aims: 1)Establish if PAK mutations are present in pancreatic Ca patient samples. 2)Establish the role of PAK-PI3K signaling in pancreatic Ca cell invasion. 3)Test our key findings using an 3D organotypic model of pancreatic Ca cell invasion. Methods. Using both patient samples and organotypic models we will characterise the PAK/PI3K interaction and in particular their role in Ca growth and metastatic spread. This will build on preliminary work that has already demonstrated the role of PAK4 in prostate Ca and ongoing research with pancreatic Ca cell-lines. Results: Once we identify the PAK/PI3K interaction and its role in pancreatic cancer, we plan to test novel PI3K/PAK inhibitors.