Gene therapy and molecular therapeutic for head and neck cancer

摘要

Despite recent progress in radiotherapy, chemotherapy and surgical techniques, the survival of patients with head and neck squamous cell carcinomas has not improved significantly over the past three decades. To conquer these malignant tumors, various new therapies have been under development, including gene therapies. In this paper, we have reviewed recent advances in gene therapies and molecular target therapy for head and neck cancers, with a special focus on the replication-selective adenovirus vector. At present, replication-defective adenovirus-based vectors have been widely used as convenient and safe vectors for transferring therapeutic genes into target cancer cells. However, these vectors have limited the efficacy of treatment by restricting the number of tumor cells to which the therapeutic gene can be delivered. Replication-selective adenoviral vectors (RSAV) are adenoviruses designed to have a limited ability to replicate themselves in the targeted tumor cells but not in other normal tissues. Tumor cell killing is achieved not by the genes delivered by the vectors but by the oncolysis induced by the replicated viruses by their original nature as adenovirus. Amplified viral vectors also spread to the adjacent tumor cells and kill these cells in the same manner. Recently, increased evidences of antitumor activity of RSAVs have been demonstrated preclinically, and several clinical trials have demonstrated the safety and clinical activity of replication-selective viruses.