CRISPR Enabled Precision Oncology: From Gene Editing to Tumor Microenvironment Remodeling

ABSTRACT Clustered regularly interspaced palindromic repeats (CRISPR) gene editing, known for its precision, is revolutionizing tumor research and treatment. This article covers the evolution of the CRISPR system from Cas9, which produces DNA double‐strand breaks, to Cas12, Cas13, base editors, and prime editors. These breakthroughs allow DNA/RNA editing, transcriptional regulation, and epigenetic reprogramming. The study encompasses CRISPR's diverse applications in tumor research, including high‐throughput screening of cancer driver genes, identification of synthetic lethal targets, and analysis of drug resistance pathways across various cancer types. It highlights CRISPR's importance in therapeutic tactics, such as targeting oncogene inactivation, restoring tumor suppressor gene activity, and engineering immune effector cells, such as CAR T and NK cells, to increase persistence, cytotoxicity, and resistance to exhaustion. This review also examines CRISPR's role in modifying the tumor microenvironment (TME), encompassing the regulation of immune checkpoints, metabolic reprogramming, and the targeted eradication of specific immunosuppressive cells. Off‐target consequences for both delivery and efficiency are discussed, along with cutting‐edge technologies including high‐fidelity Cas variants, AI‐assisted sgRNA design, and stimuli‐responsive delivery systems. Finally, the paper examines how CRISPR can be integrated with combination medicines, multimodal editing methods, and single‐cell and multiomics data to deliver tailored precision‐based interventions. This review explains the molecular logic and translational routes of CRISPR, highlighting its promise to revolutionize precision oncology.