Fragile histidine triad expression delays tumor development and induces apoptosis in human pancreatic cancer

The fragile histidine triad (FHIT) gene is a tumor suppressor gene that is altered by deletion in a large fraction of human tumors, including pancreat ic cancer, To evaluate the potential of FHIT gene therapy, we developed rec ombinant adenoviral and adenoassociated viral (AAV) FHIT vectors and tested these vectors in vitro and in vivo for activity against human pancreatic c ancer cells, Our data show that viral FHIT gene delivery results in apoptos is by activation of the caspase pathway. Furthermore, Fhit overexpression e nhances the susceptibility of pancreatic cancer cells to exogenous inducers of apoptosis, In vivo results show that FHIT gene transfer delays tumor gr owth and prolongs survival in a murine model mimicking human disease.