Gene therapy for pancreatic and biliary malignancies

Advances in our understanding of the molecular genetics of pancreatic and b iliary cancers have given us new targets for therapy using molecular and ge netic approaches. Replacement of tumour suppressor gene function using aden oviruses to transfer wild-type p53 and p16 genes can produce dramatic anti- tumour effects, both in vitro and in vivo. Blockade of dominant oncogene fu nction using dominant negative technology may have a particular application for mutated K-ras which occurs almost ubiquitously in pancreatic adenocarc inoma. Genetic prodrug activation therapy using tumour-selective gene promo ters to drive the expression of so-called suicide genes is showing remarkab le promise. Targeted delivery of such therapeutic constructs may also be po ssible through knowledge of the expression of surface receptors by particul ar tumour cell types. Genetic immunomodulation using cytokine genes as well as specific vaccines against tumour-associated antigens are now being brou ght into clinical trials.