Radioprotective gene therapy.

摘要

INTRODUCTION: Radiation-induced myelosuppression or mucositis can limit the effectiveness of radiotherapy by requiring dose reduction or delaying treatment of tumour patients. The transfer of a radioprotective gene into normal tissue cells would provide the opportunity to reduce the risks associated with haematopoietic or intestinal toxicity after irradiation. AREAS COVERED: Several potentially radioprotective genes like multidrug resistance 1 (MDR1), snail homolog 2 (SNAI2), and superoxide dismutases have been evaluated in preclinical models for their radioprotective potential in the last years. For gene transfer and ectopic expression, adenoviral, adeno-associated virus (AAV) or retroviral vectors were used. The feasibility of radioprotective gene therapy is discussed in consideration of the application of cytoprotective agents and small-molecule protectors. EXPERT OPINION: Further vector optimization for targeted cell-specific transduction and for more stable or regulated transgene expression is still required. However, radioprotective gene therapy represents a very promising method for reducing radiotherapy-related cytotoxicity of normal tissue cells and thus may improve therapy success and the patient's quality of life.