*Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
†Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K.
Biochem J. 2014 Jul 1;461(1):1-13. doi: 10.1042/BJ20140173.
Cancers arise through the progression of multiple genetic and epigenetic defects that lead to deregulation of numerous signalling networks. However, the last decade has seen the development of the concept of 'oncogene addiction', where tumours appear to depend on a single oncogene for survival. RNAi has provided an invaluable tool in the identification of these oncogenes and oncogene-dependent cancers, and also presents great potential as a novel therapeutic strategy against them. Although RNAi therapeutics have demonstrated effective killing of oncogene-dependent cancers in vitro, their efficacy in vivo is severely limited by effective delivery systems. Several virus-based RNAi delivery strategies have been explored, but problems arose associated with high immunogenicity, random genome integration and non-specific targeting. This has directed efforts towards non-viral formulations, including delivery systems based on virus-like particles, liposomes and cationic polymers, which can circumvent some of these problems by immunomasking and the use of specific tumour-targeting ligands. This review outlines the prevalence of oncogene-dependent cancers, evaluates the potential of RNAi-based therapeutics and assesses the relative strengths and weaknesses of different approaches to targeted RNAi delivery.
癌症是通过多个遗传和表观遗传缺陷的进展而产生的，这些缺陷导致众多信号网络的失调。然而，在过去的十年中，出现了“癌基因成瘾”的概念，即肿瘤似乎依赖于单个癌基因来生存。RNAi 在鉴定这些癌基因和依赖癌基因的癌症方面提供了一个非常有价值的工具，并且作为一种针对它们的新型治疗策略也具有很大的潜力。尽管 RNAi 疗法已证明在体外有效杀死依赖癌基因的癌症，但由于有效的递药系统，其在体内的疗效受到严重限制。已经探索了几种基于病毒的 RNAi 递药策略，但与高免疫原性、随机基因组整合和非特异性靶向相关的问题出现了。这促使人们努力开发非病毒制剂，包括基于病毒样颗粒、脂质体和阳离子聚合物的递药系统，通过免疫遮蔽和使用特定的肿瘤靶向配体，可以规避其中一些问题。这篇综述概述了依赖癌基因的癌症的流行情况，评估了基于 RNAi 的治疗方法的潜力，并评估了针对靶向 RNAi 递药的不同方法的相对优势和劣势。
