• CRISPR/Cas system and its applications in drug resistance Breast cancer
  • Hanieh Ataollahi,1,* Helia Ramezani,2
    1. Faculty of Biological Science, Department of Biotechnology, Islamic Azad University, North Tehran Branch, Tehran, Iran.
    2. Faculty of Biological Science, Department of Biotechnology, Islamic Azad University, North Tehran Branch, Tehran, Iran.


  • Introduction: Introduction: Many bacterial and archaea organisms use CRISPR/Cas systems (clustered regularly interspaced short palindromic repeats/CRISPR associated) to protect themselves from mobile genetic factors. These CRISPR/Cas systems are classified into six categories according to their composition and mechanism. Cancer is one of the main causes of death all around the world. It is caused by the accumulation of genetic and epigenetic modifications in 2 types of genes: tumor suppressor genes (TSG) and proto-oncogenes. In recent years, the development of CRISPR technology has revolutionized genomic engineering for cancer research ranging from basic science to translational medicine and primary cancer treatment. Breast cancer is one of the leading causes of cancer death in women worldwide, accounting for around 28% of new cancer cases. Clinical evidence indicates that drug resistance is a major barrier in the treatment of breast cancer. It makes the disease uncontrolled and leads to high mortality. Drug resistance causes breast cancer to spiral out of control and leads to high mortality, with more than 90% of treatment failures due to acquired and multidrug resistance (MDR). The development of new drugs with different targets is extremely time-consuming and expensive to avoid known resistance mechanisms. This review explains how CRISPR/Cas9 can be used to address problems associated with drug resistance in breast cancer by reversing resistance gene mutations, screening for resistance targets, and define drug therapy in breast cancer. In addition, we specifically discuss efficiency, modification of the protospacer adjacent motif (PAM), targeting selection, and application of CRISPR/Cas9.
  • Methods: Methods: The aim of this review study was to use new systems in the treatment of breast cancer and to provide solutions for drug resistance in the treatment process of this deadly cancer among women. 2010 to 2021 study was conducted. The search was performed by different keywords “CRISPR ", “CRISPR " and “CRISPR and Breast Cancer" and the articles were used based on the most appropriate titles and abstracts from various databases such as “PubMed”. “ScienceDirect”, “Springer”, “NCBI” and The results were obtained by studying the full text of the opted articles.
  • Results: Results: The emerging clinical trial has indicated that a gene-editing technique could be safe and effective in humans. US and Chinese teams intended to use CRISPR/Cas9 system in similar ways but on different types of cancers. The CRISPR/Cas9 system has been proposed as a therapeutic method to overcome drug resistance in chemotherapy-resistant cancers Blocking resistance factor(s) is an attractive strategy to further use existing anticancer agents. There are several strategies to enhance drug therapy, including altering membrane transport protein to increasing drug efflux, enhancing DNA repair and detoxification. In one study was tried to overcome doxorubicin-resistance cancer cells by using the CRISPR/Cas9 system to target MDR1. MCF-7/ADR cells were treated with doxorubicin after disruption of MDR1 by Cas9-sgRNA, and possible drug sensitivity recovery was examined. The potency of doxorubicin was enhanced in the cells treated with CRISPR/Cas9 expression construction using a proper delivery platform.
  • Conclusion: Conclusion: The use of specific targeting technologies will help us understand the mechanisms of signaling pathways such as the "genomic landscape" routes of breast cancer. Further insights into the molecular mediators of resistance will have a great impact on the ability to target genes or pathways that could overcome drug resistance for improving clinical outcomes. Therefore, although still exists technical limitations to the usage of the CRISPR/Cas9 system for targeting cancer genes in human patients, the prospects of gene therapy are nonetheless very exciting. CRISPR-based genome editing will serve as a critical tool.
  • Keywords: Keywords: CRISPR/Cas9, Breast cancer, Drug resistance