CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

Abstract

The CRISPR/Cas9 system is an RNA-based adaptive immune system in bacteria and archaea. Various studies have shown that it is possible to target a wide range of human genes and treat some human diseases, including cancers, by the CRISPR/Cas9 system. In fact, CRISPR/Cas9 gene editing is one of the most efficient genome manipulation techniques. Studies have shown that CRISPR/Cas9 technology, in addition to having the potential to be used as a new therapeutic approach in the treatment of cancers, can also be used to enhance the effectiveness of existing treatments. Undoubtedly, the issue of drug resistance is one of the main obstacles in the treatment of cancers. Cancer cells resist anticancer drugs by a variety of mechanisms, such as enhancing anticancer drugs efflux, enhancing DNA repair, enhancing stemness, and attenuating apoptosis. Mutations in some proteins of different cellular signaling pathways are associated with these events and drug resistance. Recent studies have shown that the CRISPR/Cas9 technique can be used to target important genes involved in these mechanisms, thereby increasing the effectiveness of anticancer drugs. In this review article, studies related to the applications of this technique in overcoming drug resistance in cancer cells will be reviewed. In addition, we will give a brief overview of the limitations of the CRISP/Cas9 gene-editing technique.

Keywords: CRISPR/Cas9; Cancer treatment; Chemoresistance; Gene editing; Malignancy.

Fig. 1

A summary of new advances in overcoming drug resistance in cancers

Fig. 2

Targeting an MDR-related gene by CRISPR/Cas9 system. Specific sg RNA is designed and produced to target MDR-related gene. The CRISPR system can be transferred into the cell in plasmid, mRNA, and ribonucleoprotein (RNP) complex formats. The use of viral vectors, nanoparticles, and electroporation are among the methods used to deliver the CRISPR/Cas9 system into the cell. In plasmid format, transcription and translation are required to create the sgRNA–Cas9 complex. sgRNA can direct Cas9 to the target gene, and Cas9 generates double-strand break (DBS). The NHEJ repair system then ligates the broken ends. The result of this process is disruption of the target MDR-related gene

Fig. 3

Identified genes involved in drug resistance and effects of CRISPR/Cas9-mediated inhibition on drug resistance. DR drug resistance