GENE THERAPY STRATEGIES FOR ORAL CANCER: CURRENT PROGRESS, CHALLENGES, AND FUTURE PERSPECTIVES

Gene therapy has emerged as a transformative approach in the treatment of a wide range of diseases by targeting underlying genetic defects. It involves the introduction, replacement, or modification of defective genes with functional counterparts to restore normal cellular function. This review provides an overview of the fundamental principles of gene therapy, various delivery systems, and their applications, with particular emphasis on oral cancer. Gene therapy is broadly classified into germline and somatic approaches, with somatic gene therapy being more clinically applicable. Both viral vectors—including retroviruses, adenoviruses, herpes simplex virus, and adeno-associated viruses—and non-viral delivery systems such as electroporation, gene gun, sonoporation, magnetofection, and chemical carriers are widely utilized. While viral vectors offer high transfection efficiency, they are associated with limitations such as immunogenicity, insertional mutagenesis, and restricted gene capacity. In contrast, non-viral methods are relatively safer and more scalable but often exhibit lower delivery efficiency. In the context of oral cancer, gene therapy has demonstrated promising therapeutic outcomes through strategies such as tumor suppressor gene replacement, oncolytic virotherapy, and immunomodulation. However, several challenges persist, including immune responses to vectors, inefficient gene delivery to target cells, the complexity of polygenic disorders, and the need for repeated administration. Overall, gene therapy holds significant potential as a novel therapeutic modality for oral cancer and other chronic diseases, particularly when used in combination with conventional treatments such as chemotherapy and immunotherapy.