Abstract

A wide spectrum of genetic and epigenetic variations together with environmental factors has made colorectal cancer (CRC), which involves the colon and rectum, a challenging and heterogeneous cancer. CRC cannot be effectively overcomed by common conventional therapies including surgery, chemotherapy, targeted therapy, and hormone replacement which highlights the need for a rational design of novel anticancer therapy. Accumulating evidence indicates that RNA interference (RNAi) could be an important avenue to generate great therapeutic efficacy for CRC by targeting genes that are responsible for the viability, cell cycle, proliferation, apoptosis, differentiation, metastasis, and invasion of CRC cells. In this review, we underline the documented benefits of small interfering RNAs and short hairpin RNAs to target genes and signaling pathways related to CRC tumorigenesis. We address the synergistic effects of RNAi-mediated gene knockdown and inhibitors/chemotherapy agents to increase the sensitivity of CRC cells to common therapies. Finally, this review points new delivery systems/materials for improving the cellular uptake efficiency and reducing off-target effects of RNAi. © 2020 Wiley Periodicals LLC