Progress in cancer gene therapy.

Many technical difficulties have to be overcome before effective gene therapy can be achieved. Strategies for gene therapy include 'suicide' gene therapy, transfer of a tumor suppressor gene, inhibition of activated oncogenes by antisense mechanisms, and cytokine gene transfer and tumor cell vaccination. Gene therapy will have a major impact on the healthcare of our population only when vectors are developed that can safely and efficiently be injected directly into patients as drugs. One of the most promising areas of vector development is that of non-viral vectors, which consist of liposomes, molecular conjugates, and naked DNA delivered by mechanical methods. Future research should be focused on modifying viral vectors to reduce toxicity and immunogenicity, increasing the transduction efficiency of non-viral vectors, enhancing vector targeting and specificity, regulating gene expression, and identifying synergies between gene-based agents and other cancer therapeutics. The evaluation of gene therapy combinations is another important area for future research. The identification of tumor rejection antigens from a variety of cancers and the immune response that is defective in cancer patients are important topics for future studies. A universal gene delivery system has yet to be identified, but the further optimization of each of these vectors should result in each having a unique application. Gene therapy has still a long way to go and requires the efforts of investigators in the basic and clinical sciences. Despite substantial progress, a number of key technical issues need to be resolved before gene therapy can be effectively applied in the clinic.