Application of Gene Editing Technologies in the Treatment of Colorectal Cancer: A Novel Approach in Personalized Medicine
Fatemeh Abolmashadi,1,*
1. PhD student in Pharmaceutical Chemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran
Introduction: Colorectal cancer (CRC) is among the most prevalent and lethal cancers globally. Despite advancements in traditional treatments such as surgery, chemotherapy, and radiation therapy, the rates of recurrence and drug resistance continue to pose significant challenges. In recent years, emerging technologies in gene editing, particularly the CRISPR/Cas9 system, have opened new horizons for targeted and personalized cancer therapies, including CRC. This study aims to explore the innovative applications of this technology in various aspects of colorectal cancer.
Methods: This study systematically reviews the published research on the application of gene editing technologies in the treatment of CRC. In this review, credible sources containing preclinical studies, animal models, and cellular experiments related to gene editing, signaling pathways, and epigenetic regulators have been analyzed.
Results: The application of CRISPR-Cas9 technology in colorectal cancer has led to the identification of novel therapeutic targets, including genes associated with drug resistance such as PUM1 and CYSLTR1. The knockout of these genes enhances the sensitivity of cancer cells to common drugs like trastuzumab and 5-fluorouracil. Furthermore, targeted editing of driver mutations in cancer, such as KRAS, TP53, and APC, using this technology has inhibited tumor growth in both in vivo and in vitro models. In the field of immunotherapy, the knockout of pro-inflammatory genes (such as IL-6 and IDO-1) has strengthened the anti-tumor immune response, while the genetic engineering of NK cells to express chemokine receptors (like CXCR2) has improved tumor destruction efficacy. Genomic screenings utilizing CRISPR libraries have also identified new key genes, including GRB7 (linked to resistance against MEK inhibitors) and TRAF5 (influential in resistance to oxaliplatin). Additionally, the application of the CRISPR-Cas13 system in detecting tumor and viral RNAs, along with the development of genetically edited organoid models, has enabled precise simulation of tumor progression mechanisms and personalized drug screening. Collectively, these advancements affirm the potential of CRISPR-Cas9 as a transformative tool in the pursuit of targeted therapies for colorectal cancer.
Conclusion: Consequently, gene editing technologies, particularly CRISPR/Cas9, can serve as a novel and targeted therapeutic approach in colorectal cancer. However, to translate this technology into an effective clinical treatment, further studies regarding its safety, efficacy, and precise delivery to target cells are essential.