Gene therapy for pancreatic cancer.

Gene transfer technology has the potential to revolutionize cancer treatment. Developments in molecular biology, genetics, genomics, stem cell technology, virology, bioengineering, and immunology are accelerating the pace of innovation and movement from the laboratory bench to the clinical arena. Pancreatic adenocarcinoma, with its particularly poor prognosis and lack of effective traditional therapy for most patients, is an area where gene transfer and immunotherapy have a maximal opportunity to demonstrate efficacy. In this review, we have discussed current preclinical and clinical investigation of gene transfer technology for pancreatic cancer. We have emphasized that the many strategies under investigation for cancer gene therapy can be classified into two major categories. The first category of therapies rely on the transduction of cells other than tumor cells, or the limited transduction of tumor tissue. These therapies, which do not require efficient gene transfer, generally lead to systemic biological effects (e.g., systemic antitumor immunity, inhibition of tumor angiogenesis, etc) and therefore the effects of limited gene transfer are biologically "amplified." The second category of gene transfer strategies requires the delivery of therapeutic genetic material to all or most tumor cells. While these elegant approaches are based on state-of-the-art advances in our understanding of the molecular biology of cancer, they suffer from the current inadequacies of gene transfer technology. At least in the short term, it is very likely that success in pancreatic cancer gene therapy will involve therapies that require only the limited transduction of cells. The time-worn surgical maxim, "Do what's easy first," certainly applies here.