• An effective breast cancer therapy based on CRISPR-Cas9 gene-editing tool
  • Soheil Sadr,1 Narges Lotfalizadeh,2 Ashkan Hajjafari,3 Fatemeh Heshmati,4 Hassan Borji,5,*
    1. Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
    2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
    3. Department of Pathobiology, Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
    4. Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
    5. Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran


  • Introduction: There are several factors that contribute to cancer, including genetic alterations to the cells and heterogeneous microenvironments. Cancer progression and resistance to therapy are primarily related to changes in the regulation of these genes, referred to as tumor suppressors and oncogenes. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) have shown a considerable improvement in terms of accuracy, efficiency, and specificity, which makes them very attractive over other nuclease-based tools. There has been a tremendous improvement in genome editing technologies, such as CRISPR-Cas9 systems, which are robust and programmable and have enabled genome editing to be used for cancer modeling and cancer treatment. It has been discovered that the CRISPR-Cas9 system can be exploited to discover new genes and introduce them into the gene therapy field as novel targets. It can be used as a powerful tool to introduce genes into the gene therapy field as Novel targets. The main objective of the present review is to summarize the capabilities and pitfalls of CRISPR-Cas9, as well as the potential applications for breast cancer treatment using this revolutionary technology.
  • Methods: Scopus, PubMed, ScienceDirect, and Google Scholar are some of the universally recognized databases used to retrieve published data from 2015 to 2020. CRISPR-Cas-based breast cancer treatment applications were the subject of the search strategy. Specific keywords such as “CRISPR/Cas”, “Cancer”, “Gene editing”, “Breast cancer”, and “Cancer therapy” were used. Specific keywords such as “CRISPR-Cas9”, “Cancer”, “Gene editing”, “Breast cancer”, and “Cancer therapy” were used. 1000 studies were funded. Based on abstracts, 9700 studies were omitted, and 300 went for full reading texts. Fifty relevant articles with complete abstracts were included in the study.
  • Results: Mutations in the tumor protein 53 (TP53) are found in most tumor cells. In response to internal stresses and abnormalities, p53 suppresses cell proliferation and encodes the tumor suppressor protein. Oncogene H-Ras expression in a xenograft model was shown to induce cellular transformation through CRISPR/Cas9-mediated deactivation of Transformation Related Protein 53 (TrP53). Alternatively, studies employed the CRISPR-Cas9 system to target oncogene Human Estrogen Receptor 2 (HER2). Breast cancer cells with Her2-positive exons 5, 10, and 12 found that co-expression of Cas9 and three sgRNAs reduced both cell growth and tumorigenicity. There is a strong relationship between CRISPR-Cas9 down-regulation of HER2 and the reduction of cancer risk rather than conventional therapies such as monoclonal antibodies (mAbs) mainly due to the possibility of designing new guide RNAs that could target new mutations if resistance develops. Glycoprotein epidermal growth factor receptors have an intracellular tyrosine kinase domain and are attached to cells' membranes. Mutations in the genetic code cause constitutive activation of the tyrosine kinase receptor, and this leads to the development and progression of cancer. The most effective therapies for EGFR-expressing cancers are Tyrosine Kinase Inhibitors (TKIs). However, resistance to these medications develops within two years. CRISPR-Cas9 nickase platform has been proposed by studies to repair mutated EGFR using molecular surgery through the CRISPR system. Researchers have recently been able to target epigenetic irregularities using the CRISPR-Cas9 system due to its ability to shed light on current epigenetic irregularities. As well as oncogenes encoded by viruses, the CRISPR process can be used to eliminate them.
  • Conclusion: CRISPR-Cas9 could be a game-changer for cancer treatment in the future thanks to its advantages over other genome editing techniques. The goal can be achieved through the use of CRISPR-Cas9 as an effective gene therapy tool and the identification of biomarkers that are prognostic and predictive, as well as of novel targets and pathways for signaling in breast cancer, as well as the development of new drugs. There are limitations and cautions associated with CRISPR-Cas9 that must be considered before using this tool for determining novel immune system-tumor interplays and enhancing cellular immunotherapies.
  • Keywords: Breast cancer, Cancer, CRISPR-Cas9, Gene-editing