We have previously identified a panel of drugs which preferentially kill cancer cells that are deficient in the cell-to-cell adhesion protein E-cadherin. This deficiency is the hallmark of both the familial and sporadic forms of diffuse gastric cancer (DGC). In this project, we will develop several new preclinical models for DGC, including ex-vivo stomach organoids (3D cultures). We will then use these models to test our drugs for activity as both chemoprevention compounds for the familial form and targeted therapies for the advanced, sporadic form of DGC. Chemoprevention of familial DGC has the potential to abolish the three-fold disparity that exists between the incidence of DGC in Maori and Pacifika and European New Zealanders. New targeted drugs against the sporadic form have the potential to improve the survival of up to 400,000 gastric cancer patients worldwide per year.