---
title: "Prime editing of TP53 mutations for precision tumor suppression in colorectal cancer"
id: "pubmed-42470832"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42470832"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42470832/"
doi: "10.1016/j.bbrc.2026.154311"
published_at: "2026-09-17T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Prime editing of TP53 mutations for precision tumor suppression in colorectal cancer
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42470832
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42470832/)
- **DOI:** [10.1016/j.bbrc.2026.154311](https://doi.org/10.1016%2Fj.bbrc.2026.154311)
- **Published At:** 2026-09-17T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Colorectal cancer (CRC) is a major global health problem with high mortality driven by genetic heterogeneity and therapy resistance. The tumor suppressor **TP53** is frequently mutated in CRC and contributes to genomic instability and tumor progression. - This review examines the potential of **prime editing**, a programmable search-and-replace genome engineering method, to correct TP53 mutations in CRC as a precision oncology strategy. - Prime editing avoids two double-stranded DNA breaks, reducing insertions/deletions (indels) and enabling more precise edits than conventional CRISPR-Cas9 approaches. - Newer prime editing platforms and tools discussed include **PEmax**, PE5/PE5max, engineered pegRNAs, twin prime editors, PrimeDel, and PASTE, which extend efficiency, editing range, and flexibility. - TP53 hotspot variants cited as candidates for repair include R175H, R248Q/W, R273H/C, and R282W based on hotspot and organoid studies referenced in the review. - The review highlights translational challenges: large cargo size, delivery specificity to tumor cells, intratumoral heterogeneity, variable editing efficiency, immune recognition of editing cargo, and off-target risks. - Organoid models and hotspot-focused studies are noted as important preclinical validation tools, but optimized delivery systems and comprehensive safety testing are required before clinical application. - The authors conclude that prime editing holds promise for CRC treatment but emphasize the need for further optimization of delivery, rigorous preclinical evaluation, and safety monitoring for therapeutic adoption. - The review consolidates TP53 biology, recent prime editing advances, and CRC-specific translational barriers, and proposes a stepwise approach toward clinical translation.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 18. # Precision prime editing of TP53 mutations for functional tumor suppression in colorectal cancer [Md Azhar](https://pubmed.ncbi.nlm.nih.gov/?term=Azhar+M&cauthor_id=42470832)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-1 "School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India."), [Rishabha Malviya](https://pubmed.ncbi.nlm.nih.gov/?term=Malviya+R&cauthor_id=42470832)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-2 "School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. Electronic address: rishabhamalviya19@gmail.com."), [Phool Chandra](https://pubmed.ncbi.nlm.nih.gov/?term=Chandra+P&cauthor_id=42470832)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-3 "Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, 244001, India."), [Sathvik Belagodu Sridhar](https://pubmed.ncbi.nlm.nih.gov/?term=Sridhar+SB&cauthor_id=42470832)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-4 "College of Pharmacy, Dubai Medical University, Dubai, United Arab Emirates."), [Javedh Shareef](https://pubmed.ncbi.nlm.nih.gov/?term=Shareef+J&cauthor_id=42470832)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-5 "RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates."), [Tarun Wadhwa](https://pubmed.ncbi.nlm.nih.gov/?term=Wadhwa+T&cauthor_id=42470832)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#full-view-affiliation-5 "RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates.") Affiliations Expand ### Affiliations * 1 School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. * 2 School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. Electronic address: rishabhamalviya19@gmail.com. * 3 Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, 244001, India. * 4 College of Pharmacy, Dubai Medical University, Dubai, United Arab Emirates. * 5 RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates. * PMID: **42470832** * DOI: [ 10.1016/j.bbrc.2026.154311 ](https://doi.org/10.1016/j.bbrc.2026.154311) Item in Clipboard Review # Precision prime editing of TP53 mutations for functional tumor suppression in colorectal cancer Md Azhar et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) . 2026 Sep 17:831:154311. doi: 10.1016/j.bbrc.2026.154311. Epub 2026 Jul 18. ### Authors [Md Azhar](https://pubmed.ncbi.nlm.nih.gov/?term=Azhar+M&cauthor_id=42470832)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-1 "School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India."), [Rishabha Malviya](https://pubmed.ncbi.nlm.nih.gov/?term=Malviya+R&cauthor_id=42470832)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-2 "School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. Electronic address: rishabhamalviya19@gmail.com."), [Phool Chandra](https://pubmed.ncbi.nlm.nih.gov/?term=Chandra+P&cauthor_id=42470832)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-3 "Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, 244001, India."), [Sathvik Belagodu Sridhar](https://pubmed.ncbi.nlm.nih.gov/?term=Sridhar+SB&cauthor_id=42470832)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-4 "College of Pharmacy, Dubai Medical University, Dubai, United Arab Emirates."), [Javedh Shareef](https://pubmed.ncbi.nlm.nih.gov/?term=Shareef+J&cauthor_id=42470832)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-5 "RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates."), [Tarun Wadhwa](https://pubmed.ncbi.nlm.nih.gov/?term=Wadhwa+T&cauthor_id=42470832)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42470832/#short-view-affiliation-5 "RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates.") ### Affiliations * 1 School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. * 2 School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., 201308, India. Electronic address: rishabhamalviya19@gmail.com. * 3 Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, 244001, India. * 4 College of Pharmacy, Dubai Medical University, Dubai, United Arab Emirates. * 5 RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates. * PMID: **42470832** * DOI: [ 10.1016/j.bbrc.2026.154311 ](https://doi.org/10.1016/j.bbrc.2026.154311) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Colorectal cancer (CRC) is a major global health concern, with high mortality due to genetic heterogeneity and resistance to treatment. Tumor Protein p53 (TP53) mutations are also among the most important molecular changes that can disrupt genomic stability and facilitate tumor progression, so it is a critical target for precision-based interventions. **Aim:** This review aims to discuss the future potential of prime editing as a new generation of genome engineering to identify precise approaches to correct TP53 mutations in colorectal cancer. **Method:** A focused literature review was conducted on PubMed, Scopus, Web of Science, and Google Scholar for articles published between the years of 2010 and 2026. The keywords used in the search were CRC, TP53 mutation, prime editing, Prime Editing Guide RNA (pegRNA), CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9), and precision oncology. Studies were screened for experimental, mechanistic, and translational, and the focus was on mutation-specific editing, delivery platforms, organoid validation, clinically relevant barriers, etc. RESULTS/DISCUSSION: Prime editing is a programmable search-and-replace method that does not involve two single-stranded Deoxyribonucleic Acid (DNA) breaks, resulting in fewer Insertions/deletions (indels) and greater precision compared with traditional CRISPR-Cas9 approaches. Recent systems like Prime Editor Max (PEmax), PE5/PE5max, engineered pegRNAs, twin prime editors, PrimeDel, and PASTE have enhanced the efficiency, range, and flexibility. Hotspot and organoid studies suggest that variants of TP53, particularly R175H, R248Q/W, R273 H/C, and R282W, can be repaired. But cargo size, delivery specificity, tumor heterogeneity, varying cargo editing efficiency, cargo recognition by the immune system, and off-target risk are all barriers to clinical translation. **Conclusion:** Precision oncology with prime editing has the potential to be a useful tool for CRC, though optimized delivery, thorough preclinical testing, and safety monitoring will be required for therapeutic adoption. **Originality:** This review combines TP53 hotspot biology, recent breakthroughs in prime editing technology, and CRC-specific translational challenges, and provides a step-by-step approach to its clinical application in a unique way. **Keywords:** Allele-specific editing; Colorectal cancer; Gene therapy; Prime editing; TP53 mutation; pegRNA. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest No financial/personal relationship. ## Similar articles * [ Application of prime editing system to introduce TP53 R248Q hotspot mutation in acute lymphoblastic leukemia cell line. ](https://pubmed.ncbi.nlm.nih.gov/38549229/) Nguyen T, Aida T, Iijima-Yamashita Y, Tamai M, Nagamachi A, Kagami K, Komatsu C, Kasai S, Akahane K, Goi K, Inaba T, Sanada M, Inukai T.Nguyen T, et al.Cancer Sci. 2024 Jun;115(6):1924-1935. doi: 10.1111/cas.16162. Epub 2024 Mar 28.Cancer Sci. 2024.PMID: 38549229Free PMC article. * [ Prime Editing, CRISPR-Cas9, and NanoCas Genome Editing for Cancer Treatment. ](https://pubmed.ncbi.nlm.nih.gov/41495582/) Hossain H, Sayeed SSB, Islam S, Ahmad T, Brishty KA, Chowdhury MSR, Alam MS, Mahmud MS, Rahman MM.Hossain H, et al.Mol Biotechnol. 2026 Jun;68(6):2630-2658. doi: 10.1007/s12033-025-01548-9. Epub 2026 Jan 6.Mol Biotechnol. 2026.PMID: 41495582Review. * [ Genome Editing in Gynecological Oncology: The Emerging Role of CRISPR/Cas9 in Precision Cancer Therapy. ](https://pubmed.ncbi.nlm.nih.gov/40394347/) Kumar N.Kumar N.Ther Innov Regul Sci. 2025 Sep;59(5):937-948. doi: 10.1007/s43441-025-00807-w. Epub 2025 May 20.Ther Innov Regul Sci. 2025.PMID: 40394347Review. * [ Prime Editing: The Next Frontier in Precision Gene Therapy. ](https://pubmed.ncbi.nlm.nih.gov/41038616/) Aliciaslan M, Erbasan E, Erendor F, Sanlioglu S.Aliciaslan M, et al.J Gene Med. 2025 Oct;27(10):e70040. doi: 10.1002/jgm.70040.J Gene Med. 2025.PMID: 41038616Review. * [ Gene Therapy with CRISPR/Cas9 Coming to Age for HIV Cure. ](https://pubmed.ncbi.nlm.nih.gov/29019352/) Soriano V.Soriano V.AIDS Rev. 2017 Oct-Dec;19(3):167-172.AIDS Rev. 2017.PMID: 29019352 [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42470832) ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * CRISPR-Cas Systems Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22CRISPR-Cas+Systems%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=CRISPR-Cas+Systems) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Colorectal Neoplasms* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Colorectal+Neoplasms%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Colorectal+Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Colorectal Neoplasms* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Colorectal+Neoplasms%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Colorectal+Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Gene Editing* / methods Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Editing%2Fmethods%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Editing) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Genetic Therapy / methods Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Genetic+Therapy%2Fmethods%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Genetic+Therapy) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Mutation* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mutation%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mutation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Precision Medicine / methods Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Precision+Medicine%2Fmethods%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Precision+Medicine) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42470832/) * Tumor Suppressor Protein p53* / genetics Actions * [ Search in PubMed ](https://pubm
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