CRISPR-Cas9 in Cancer Therapy: Therapeutic Strategies, Delivery Systems, and Immuno-oncology Applications

Abstract

Cancer genomics has transformed the field of oncology, with cancer now considered a highly heterogeneous and genetically complex disease driven by a variety of somatic and germline alterations. This complexity, which includes mutations in oncogenes and tumor suppressor genes, often undermines conventional therapies and leads to drug resistance and relapse, underscoring the critical need for precision medicine. CRISPR-Cas9 system is a revolutionary gene-editing technology that can overcome these challenges by allowing for precise, efficient, and programmable genome modification. Here, the study reviews the different applications of CRISPR-Cas9 in cancer research and therapy. It highlights its foundational role in creating advanced in vitro and in vivo cancer models, enabling the accurate reproduction of tumor biology and the performance of mechanistic studies. Also discussed is the utility of CRISPR-based functional genomic screens to identify novel therapeutic targets and resistance mechanisms. Therapeutically, CRISPR-Cas9 provides promising strategies such as direct gene modification for oncogene inactivation, tumor suppressor restoration, and reversal of multidrug resistance. The most advanced clinical application of it is in immunotherapy, especially the engineering of improved CAR-T cells and other immune effectors. In addition, CRISPR-targeted tumor microenvironment and oncogenic virus offer new strategies for cancer treatment. The problems of off-target effects, delivery challenges, and ethical concerns are serious obstacles despite its enormous potential. Progress in delivery systems and genome-editing precision, as well as in clinical trials, continues to advance CRISPR-Cas9 to become part of routine oncology practice, and to drive forward the paradigm of personalized cancer therapy.