Challenges and opportunities for siRNA-based cancer treatment. (28th February 2017)

• Record Type: Journal Article
• Authors: Wang, Tao; Shigdar, Sarah; Shamaileh, Hadi Al; Gantier, Michael P.; Yin, Wang; Xiang, Dongxi; Wang, Lan; Zhou, Shu-Feng; Hou, Yingchun; Wang, Peng; Zhang, Weihong; Pu, Chunwen; Duan, Wei
• Is Part Of: Cancer letters. Volume 387(2017)
• Page Start: 77
• Page End: 83
• Publication Date: 2017-02-28
• Subjects: RNA interference -- Tumour -- Nanoparticle -- EPR effect -- Endosome escape -- Off-target; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.03.045
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Distinct rules for chemical modification of siRNA and antisense oligonucleotide. Optimised research model leads to predictable bio-distribution pattern of siRNAs. Characterisation of endosomal escape aids future siRNA-based cancer treatment. Gene target selection – cancer stem cell critical genes and multiple gene targeting. Appropriate research controls and 5′RACE assay ensure minimum off-target effect. Abstract: 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.