The role of gene therapy in combined modality treatment strategies for cancer

Multimodality therapy has been widely used in cancer treatment for enhancing efficacy, reducing toxicity, and preventing or delaying development of resistance. However, as the difference in biochemical signals between normal and malignant cells is usually trivial, combinations of conventional therapies often cause intolerably high levels of toxicity in most cancer patients. Gene therapy uses genetically encoded functions to attack molecular events involved in the development and maintenance of malignancies, providing a molecular approach to eradicate cancer cells or to protect normal cells from the toxicity of conventional therapies. Furthermore, gene therapy can also be used to augment biochemical signals required for effective chemotherapy and radiotherapy. Recent preclinical studies have shown that synergistic effects can be achieved by combining gene therapy and conventional anticancer therapies. Moreover, several phase I/II clinical studies have demonstrated that anticancer gene therapy is well tolerated and that combining gene therapy with chemotherapy, radiotherapy, or both, resulted in enhanced antitumor activity without increased toxicity. Favorable clinical responses, including a pathologically complete response, have been reported in a subset of patients with advanced disease or with cancers resistant to chemotherapy or radiotherapy. Thus, combining gene therapy and conventional therapies may provide an improvement in the treatment of cancers, especially for those resistant to conventional therapies. This review focuses on the most recent achievements in cancer treatment by combining gene therapy with conventional therapies.