AI-driven CRISPR strategies in breast cancer: Organoid modeling, adaptive editing, and precision delivery

Articles in Press

Document Type : Review Article

Authors

1 Department of Radiology Techniques, Health and Medical Techniques College, Alnoor University, Nineveh, Iraq

2 Ahl al bayt University, Kerbala, Iraq

3 University institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India

4 Modern College of Business and Science, Muscat, Oman

5 On sabbatical leave, from Jordan University of Science and Technology, Irbid, Jordan

6 Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India

7 Center for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India

8 Department of General Medicine, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), Bhubaneswar, Odisha-751003, India

9 Uttaranchal Institute of Pharmaceutical Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India

10 Department of Skin and Venereal Diseases, Samarkand State Medical University, Samarkand, Uzbekistan

11 Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001, Iraq

12 Gilgamesh Ahliya University, Baghdad, Iraq

13 Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq

14 Pharmacy college, Al-Farahidi University, Baghdad, Iraq

10.22038/ijbms.2026.90248.19456

Abstract

Triple-negative breast cancer (TNBC) is defined by profound heterogeneity, dormant metastatic reservoirs, and rapid therapy resistance. Building on our AI-Driven CRISPR Strategies in Breast Cancer framework, CRISPR–Cas9 is emerging as more than a gene-editing tool, capable of restoring circadian integrity, eliminating dormant clones, and re-programming immune surveillance. A structured PubMed, Scopus, and ClinicalTrials.gov review through 2025 integrated mechanistic, preclinical, and early clinical evidence. Beyond standard knockout, base, and prime editing, we highlight chrono-genomic repair of BMAL1/PER2, dormancy-focused synthetic-lethality screens, and genomic-collapse tactics for BRCA1-deficient tumors. Adaptive AI pipelines that iteratively refine guide RNAs and exosome-mimetic carriers, incorporating Boolean logic gates, were also evaluated for self-regulated, tumor-specific delivery. Proof-of-concept studies show that HER2 deletion, TP53 rescue, and ABCB1 silencing enhance chemosensitivity across luminal, HER2-positive, and TNBC models. Circadian restoration expands therapeutic windows and delays relapse in xenografts. Dormancy-directed CRISPR screens reveal unique vulnerabilities in disseminated tumor cells, whereas genomic collapse selectively destroys BRCA1-mutant clones. Integration with CAR-T cells and antibody–drug conjugates amplifies cytotoxicity, and transient nanoparticle or exosome systems improve solid-tumor penetration while minimizing off-target events. CRISPR–Cas9 is transitioning from a molecular scalpel to an adaptive, self-learning therapeutic ecosystem. By uniting AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery, the strategies detailed here define a next-generation precision-oncology paradigm capable of anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse.

Keywords

Main Subjects

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Iranian Journal of Basic Medical Sciences

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