Lara-Guerra Humberto, Roth Jack A
Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Crit Rev Oncog. 2016;21(1-2):115-24. doi: 10.1615/CritRevOncog.2016016084.
Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein.
基因治疗最初旨在治疗单基因疾病。从理论上讲,用功能正常的基因替换缺陷基因可以治愈疾病。在癌症中,存在多种基因缺陷,并且在疾病过程中分子特征会发生变化,这使得替换所有缺陷基因成为不可能。为了克服这些困难,人们采用了各种基因治疗策略,包括免疫刺激、自杀基因转移、驱动癌基因抑制、介导细胞凋亡或抗血管生成肿瘤抑制基因的替换,以及增强放疗和化疗等传统治疗的基因转移。其中一些策略已在非小细胞肺癌患者中成功进行了测试,本文将对实验室研究和临床试验的结果进行综述。