Mini-reviewChallenges and opportunities for siRNA-based cancer treatment

- 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.

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.