Replacement and suicide gene therapy for targeted treatment of lung cancer.

Lung cancer is the leading cause of cancer-related death in the developed world; consequently, novel therapeutic strategies are in high demand. A major problem with the present treatment modalities is the lack of tumor specificity giving rise to dose-limiting toxicity and side effects. Gene therapy constitutes an experimental approach gaining increased attention as a putative future cancer therapeutic strategy. Using this strategy, cancer cytotoxicity can be obtained by replacing mutated genes with functional analogues or introducing a suicide gene into the malignant cells. Insight into the molecular biology of cancer cells has identified a number of regulatory gene sequences, which can be used to selectively activate the therapeutic gene specifically in cancer cells, thereby reducing nonspecific toxicity. Although further improvements are necessary, recent encouraging results have shown promise for future clinical application of gene therapy. This article presents an update on the experimental and clinical results obtained within the field of lung cancer gene therapy, concentrating on strategies to specifically activate expression of the therapeutic gene in cancer cells. Furthermore, status of the development of delivery vector constructs for lung cancer gene therapy will be presented.