Targeted Epigenome Editing with CRISPR Technologies: Transforming Cancer Treatment Strategies

Background: Cancer remains a leading global health challenge, with nearly 10 million deaths in 2020. Traditional therapies like chemotherapy and radiation often face limitations, including systemic toxicity, acquired resistance, and suboptimal tumor targeting. The advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 technology has revolutionized genetic research by enabling precise gene editing. Its adaptation for epigenetic modulation presents novel opportunities to reversibly regulate gene expression in cancer without introducing permanent deoxyribonucleic acid (DNA) alterations. Objective: This literature review evaluates the therapeutic potential of CRISPR-based epigenetic editing in cancer treatment and examines recent clinical studies that inform its translational prospects. Methodology: A systematic literature search was conducted using PubMed for clinical trials and randomized controlled trials published between January 2020 and June 2025, focusing on CRISPR, epigenetics, and cancer therapy. Five clinical studies met the inclusion criteria and were reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Results: The reviewed studies highlight genetic mutations and epigenetic alterations in cancers such as human epidermal growth factor receptor 2 (HER2)-mutant breast cancer, prostate cancer, and peripheral T-cell lymphomas. CRISPR-dCas9 fusion tools and ribonucleic acid (RNA)-targeting systems like Cas13 offer precision in modulating gene expression, potentially overcoming drug resistance and reactivating tumor suppressors. However, efficient delivery, specificity, and safety remain significant barriers. Conclusion: CRISPR-mediated epigenetic editing holds transformative potential in precision oncology by enabling targeted, reversible gene regulation. Future research must address delivery technologies, off-target risks, and clinical validation to advance CRISPR applications in cancer therapeutics.