Gene therapy for pancreatic and biliary malignancies

Advances in our understanding of the molecular genetics of pancreatic and biliary cancers have given us new targets for therapy using molecular and genetic approaches. Replacement of tumour suppressor gene function using adenoviruses to transfer wild-type p53 and p16 genes can produce dramatic anti-tumour effects, both in vitro and in vivo. Blockade of dominant oncogene function using dominant negative technology may have a particular application for mutated K-ras which occurs almost ubiquitously in pancreatic adenocarcinoma. Genetic prodrug activation therapy using tumour-selective gene promoters to drive the expression of so-called suicide genes is showing remarkable promise. Targeted delivery of such therapeutic constructs may also be possible through knowledge of the expression of surface receptors by particular tumour cell types. Genetic immunomodulation using cytokine genes as well as specific vaccines against tumour-associated antigens are now being brought into clinical trials.