INTERNATIONAL CONGRESS OF
CancerGenetics
Base Editing Approaches for Correcting TP53 and KRAS Mutations in Colorectal Cancer: A Systematic Review
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Yekta Rezapour,1 AmirMohammad Ganjali,2 Hossein Javid,3,*
1. Student Research Committee, Varastegan Institute for Medical Sciences, Mashhad, Iran
2. Student Research Committee, Varastegan Institute for Medical Sciences, Mashhad, Iran
3. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
- Introduction: Colorectal cancer is one of the most common and deadly cancers in the world. Colorectal cancer (CRC) is affected by a set of frequent mutations, among which TP53 and KRAS are the most frequent and clinically significant. Targeted treatments aim to address these mutations as a viable approach. New genetic engineering technologies, especially CRISPR-based methods and especially base editing, have enabled the precise correction of point mutations. These methods operate without causing DNA double-strand breaks and have fewer side effects than more traditional methods. This study aims to investigate the use of base editing in the correction of TP53 and KRAS mutations in colorectal cancer.
- Methods: We performed a methodical search of the PubMed, Scopus, and ScienceDirect databases for papers that came out between 2020 and 2025. After reviewing about 23 publications, we selected and included 23 that met the inclusion criteria in the final analysis of the review.
- Results: Cytosine base editors (CBE) and adenine base editors (ABE) have been used successfully to eliminate point mutations in human cells that are linked to TP53 and KRAS. With CBE, it was possible to change the C-G base pair to T-A in cells that had TP53 mutations. This change brought the p53 protein back to its natural state and made it work better as a tumor suppressor. Using CBE to target TP53 mutations brought back some of the activity of p53 in models of colorectal cancer. Functional experiments have demonstrated that base editing in colorectal cells can restore p53 transcriptional activity. Scientists have used ABEmax to fix the common G12D mutation at codon 12 in colorectal cancer cells that had KRAS. Fixing the KRAS mutation made the signaling normal again and slowed down the proliferation of cells. There were remarkably few side effects from these adjustments, and they were highly accurate. These findings suggest that base editing technology possesses significant potential to enhance tumor suppressor functionality.
- Conclusion: Using simple editing methods to change KRAS and TP53 mutations in colorectal cancer has shown potential. These methods are more precise and have fewer issues than the traditional CRISPR-Cas9 system. In the lab, it has been shown that open editing in cells with a TP53 mutation makes them more sensitive to chemotherapy. Improving responsiveness to fluorouracil and oxaliplatin will enhance synergy. Future research should focus on optimizing transfer methods and assessing the safety and efficacy of intravenous medications. These actions are crucial for applying Base Editing in the treatment of colorectal cancer.
- Keywords: Gene Editing, Colorectal Neoplasms, Proto-Oncogene Proteins p21, Tumor Suppressor Protein p53
