Gene Silencing Strategies in Cancer Therapy: An Update for Drug Resistance

Abstract

RNAi, post-transcriptional gene silencing mechanism, could be considered as one of the most important breakthroughs and rapidly growing fields in science. Researchers are trying to use this discovery in the treatment of various diseases and cancer is one of them although there are multiple treatment procedures for treatment-resistant cancers, eradication of resistance remain as an unsolvable problem yet. The current review summarizes both transcriptional and post-transcriptional gene silencing mechanisms, and highlights mechanisms leading to drug-resistance such as, drug efflux, drug inactivation, drug target alteration, DNA damages repair, and the epithelial-mesenchymal transition, as well as the role of tumor cell heterogeneity and tumor microenvironment, involving genes in these processes. It ultimately points out the obstacles of RNAi application for in vivo treatment of diseases and progressions that have been achieved in this field.

Keywords: Drug resistance; RNA interference; cancer; gene silencing; post-transcriptional gene; treatment-resistant cancers..