Malek Anastasia, Tchernitsa Oleg
Laboratory of Experimental Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Methods Mol Biol. 2010;623:423-36. doi: 10.1007/978-1-60761-588-0_27.
Ovarian cancer is the most lethal neoplasm of the female genital tract. Despite progress with chemotherapy, surgery and supportive care, the death rate remains extremely high. Gene silencing therapy represents a possible opportunity to advance the management of ovarian cancer patients. The concept of gene silencing therapy, which is based on RNA interference (RNAi) phenomenon, requires selection of targeted genes and development of a strategy for genetic drug development. Recently, plenty of research studies in ovarian cancer genetics have been published. Although they can be analyzed regarding candidate gene selection, the therapeutic effect of particular gene silencing can only be evaluated experimentally at this time. Obviously, the correct choice and application of a genetic drug delivery system determines the efficacy of gene silencing. Complexation of therapeutic nucleic acids with cationic polymers, cationic lipids, or their combination, represents a main strategy of non-virus-mediated delivery of genetic drug. Owing to a tendency of ovarian cancer to spread through the abdominal cavity, a delivery system should allow intraperitoneal mode of administration. Therefore, clinical application of RNAi may rely on a combination of biosciences and nanotechnology: in particular, identifying optimal small interfering RNAs (siRNAs) against optimal target genes and developing an efficient system for siRNA delivery into the cancer cells.
卵巢癌是女性生殖道中最致命的肿瘤。尽管在化疗、手术和支持治疗方面取得了进展，但死亡率仍然极高。基因沉默疗法为推进卵巢癌患者的治疗提供了一个可能的契机。基于RNA干扰（RNAi）现象的基因沉默疗法概念，需要选择靶向基因并制定遗传药物开发策略。最近，发表了大量关于卵巢癌遗传学的研究。虽然可以对它们进行候选基因选择分析，但目前只能通过实验评估特定基因沉默的治疗效果。显然，遗传药物递送系统的正确选择和应用决定了基因沉默的效果。治疗性核酸与阳离子聚合物、阳离子脂质或它们的组合形成复合物，是遗传药物非病毒介导递送的主要策略。由于卵巢癌有通过腹腔扩散的倾向，递送系统应允许腹腔内给药。因此，RNAi的临床应用可能依赖于生物科学和纳米技术的结合：特别是，针对最佳靶基因鉴定最佳小干扰RNA（siRNA），并开发一种将siRNA有效递送至癌细胞的系统。
