Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Nat Rev Drug Discov. 2015 Dec;14(12):843-56. doi: 10.1038/nrd4685. Epub 2015 Nov 16.
Small interfering RNA (siRNA)-based therapies are emerging as a promising new anticancer approach, and a small number of Phase I clinical trials involving patients with solid tumours have now been completed. Encouraging results from these pioneering clinical studies show that these new therapeutics can successfully and safely inhibit targeted gene products in patients with cancer, and have taught us important lessons regarding appropriate dosages and schedules. In this Review, we critically assess these Phase I studies and discuss their implications for future clinical trial design. Key challenges and future directions in the development of siRNA-containing anticancer therapeutics are also considered.
基于小干扰 RNA（siRNA）的治疗方法作为一种有前途的新型抗癌方法正在兴起，目前已经完成了少数涉及实体瘤患者的 I 期临床试验。这些开创性临床研究的令人鼓舞的结果表明，这些新型疗法可以成功且安全地抑制癌症患者的靶向基因产物，并为我们提供了有关适当剂量和方案的重要经验教训。在这篇综述中，我们批判性地评估了这些 I 期研究，并讨论了它们对未来临床试验设计的影响。还考虑了含有 siRNA 的抗癌治疗药物开发中的关键挑战和未来方向。
