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.

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

“…Studies on cellular and animal models have shown that the CRISPR/Cas9 technique can be effective in treating cancers [ 320 ]. For this reason, several clinical trials are underway to evaluate the efficiency of this technology in treating cancers [ 321 , 322 ]. While no treatment is available using this system, a recent study showed that decreasing MYCN copy number by using MYCN-A3 alkylating agent can down-regulate MYCN expression and suppress NB growth in vitro and in a xenograft mouse model [ 323 ].…”

Evolution-Informed Strategies for Combating Drug Resistance in Cancer

“…To further enhance our understanding of the evolution of drug resistance in cancer, technologies, such as CRISPR/Cas, clonal tracing, or spatial analyses, can be applied to experimental evolution. The CRISPR/Cas system can be used to characterize potentially different mechanisms of resistance against a drug [ 73 ]. For instance, this could be applied to the Ewing’s sarcoma experiment described above.…”

Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets

“…Gene editing can also serve as a therapeutic tool for reducing chemoresistance by knocking in or knocking out associated genes. Gene editing as an approach to overcome drug resistance has been thoroughly reviewed elsewhere [ 224 ]. Briefly, total removal of a gene correlated to resistance would provide more of a long-term response in comparison to RNAi-based therapies and has been shown to provide therapeutic benefits in ovarian cancer.…”