School of Nursing, Zhengzhou University, Zhengzhou 450001, China; School of Medicine, Deakin University, 75 Pigdons Road, Waurn Ponds, Victoria 3217, Australia.
School of Medicine, Deakin University, 75 Pigdons Road, Waurn Ponds, Victoria 3217, Australia.
Cancer Lett. 2017 Feb 28;387:77-83. doi: 10.1016/j.canlet.2016.03.045. Epub 2016 Apr 1.
As one of the life-threatening diseases involving multi-step genetic and epigenetic disorders, cancer has long been a dynamic research area for siRNA-based therapy as half of the current siRNA-based clinical trials are involved in oncology. However, despite consistent enthusiasm in the academic world, siRNA-based cancer treatment still faces obstacles and difficulties in clinical development. In this article, we discuss key challenges facing siRNA-based cancer treatment revealed from recent clinical and preclinical studies, including chemical modification, tumour penetration, endosomal escape, target selection and off-target effects. In addition, opportunities and avenues for translating siRNA technology from bench to oncologic clinics are explored.
作为涉及多步遗传和表观遗传紊乱的危及生命的疾病之一,癌症一直是基于 siRNA 治疗的充满活力的研究领域,因为目前一半的基于 siRNA 的临床试验都涉及肿瘤学。然而,尽管学术界一直保持着热情,但基于 siRNA 的癌症治疗在临床开发中仍然面临障碍和困难。在本文中,我们讨论了最近的临床前和临床研究中揭示的基于 siRNA 的癌症治疗所面临的关键挑战,包括化学修饰、肿瘤穿透、内涵体逃逸、靶标选择和脱靶效应。此外,还探讨了将 siRNA 技术从实验室转化为肿瘤临床的机会和途径。