Progress in gene therapy for oral cancer

This chapter reviews the principle, transfer techniques, therapeutic strategies, preclinical and clinical applications and limitations of gene therapy in the management of oral squamous cell carcinoma (SCC) or oral cancer. Viruses have typically been the most used transfer system for the delivery of oral cancer gene therapy. The viral vectors commonly used and reviewed in this chapter are: adenoviruses, adenoassociated viruses, lentiviruses, and retroviruses, although other viruses and nonviral gene transfer systems are also discussed. Transfection of oral tumors in vivo with gene therapy has been accomplished mostly by direct intralesional administration to date, and sometimes by topical application. Some approaches have been translated and phase I and II clinical trials have established the safety and clinical efficacy of gene therapy in the treatment of oral cancer in humans, especially in combination with chemotherapy or radiotherapy. Phase III clinical trials as well as the application of gene therapy as an adjuvant following surgery are presently underway. Therefore, gene therapy has great promise as an innovative approach to the treatment of oral cancer especially in recurrent disease and as an adjuvant treatment. In fact, oral SCC is an excellent tumor target due to its frequent genetic mutations and relative localized nature that render them highly accessible for intratumoral administration of gene therapy.Future gene therapy strategies will develop towards systemic delivery of vectors in oral cancer patients, with the goal of controlling regional and metastatic lesion growth. Gene therapy strategies will continue to be explored, developed, and refined to achieve better translation potential and efficacy over time.We foresee that tumor-targeted delivery systems will allow systemic therapies to have a wide therapeutic reach for controlling or eliminating micrometastases of oral cancer in lymphnodes and/or distant sites, potentially reducing the mortality associated with this disease.