Kirby Tyler O, Curiel David T, Alvarez Ronald D
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 35233-7333, USA.
Hematol Oncol Clin North Am. 2003 Aug;17(4):1021-50. doi: 10.1016/s0889-8588(03)00055-8.
Gene therapy remains a promising therapeutic modality for ovarian cancer. Yet much work remains to be done to see gene therapy realize its full potential in elucidating the complex genetic interactions of delivered genes within target cancer cells and in the development of improved vector systems. Because most neoplasms involve multiple mutations, the targeting of a single mutation is unlikely to achieve total tumor control: gene therapy strategies that target multiple cellular processes or invoke various antitumor approaches need to be investigated. Additionally, current vector systems do not transduce ovarian cancer cells efficiently and are hampered by immune responses that further limit their efficacy. Additionally, limitations in vector specificity lead to transduction of normal cells and subsequent toxicity. Investigators are developing refinements to current gene therapy approaches that would address these limitations and that are soon to be incorporated into clinical trials. It is hoped that these advances will lead to improvements in the therapeutic index for ovarian cancer gene therapy and provide another effective therapeutic tool for this deadly disease.
基因治疗仍然是卵巢癌一种很有前景的治疗方式。然而，要使基因治疗在阐明导入基因在靶癌细胞内复杂的基因相互作用以及改进载体系统的开发方面充分发挥其潜力，仍有许多工作要做。由于大多数肿瘤涉及多种突变，针对单一突变进行靶向治疗不太可能实现对肿瘤的完全控制：需要研究针对多个细胞过程或采用各种抗肿瘤方法的基因治疗策略。此外，目前的载体系统不能有效地转导卵巢癌细胞，并且受到免疫反应的阻碍，这进一步限制了它们的疗效。此外，载体特异性的局限性导致正常细胞的转导及随后的毒性。研究人员正在对当前的基因治疗方法进行改进，以解决这些局限性，并很快将纳入临床试验。希望这些进展将提高卵巢癌基因治疗的治疗指数，并为这种致命疾病提供另一种有效的治疗工具。
