CRISPR/Cas9 in cancer research and therapeutics: Clinical applications, optimization strategies, and future perspectives

CRISPR/Cas9 as a multifaceted platform in oncology: From mechanistic insights and delivery innovations to therapeutic applications (direct tumor editing, oncolytic viruses, and engineered immunotherapies), liquid biopsy-based detection, and clinical translation. The schematic highlights key opportunities and persistent bottlenecks, including off-target effects, tissue-specific delivery, and ethical considerations, that shape the future of precision cancer medicine. • CRISPR/Cas9 facilitates high-precision genetic manipulation in preclinical cancer models, enabling functional validation of oncogenes and tumor suppressors. • Targeted therapy using CRISPR shows potential for personalized oncology. • CRISPR-based tools enhance drug sensitivity in resistant tumors. • In vivo studies demonstrate tumor suppression via CRISPR-mediated gene knockdown. • Exosome-delivered CRISPR systems offer novel cancer treatment strategies. Genome editing tools have provided researchers and clinicians with an invaluable opportunity to understand and treat various disorders. These tools can potentially be used to precisely, efficiently, and safely treat disorders with genetic components. Among these disorders, are different malignancies. CRISPR/Cas9 has evolved to be the method of choice for most genome editing applications since it is much easier to work with. It can modify the aberrant sequence of oncogenes and tumor suppressor genes. It can also be used to design and optimize oncolytic viruses and immunotherapies with great accuracy. In the field of cancer research, it can be used to detect possible drug targets, mechanisms of drug resistance, and design cancer models such as cell lines, organoids, and even whole animals. However, the widespread application of this therapy has been limited because of its possible off-target activity and difficulties associated with its delivery to a specific site. Different approaches have been implemented to compensate for these shortcomings which are discussed in detail in this paper. With the incredible pace of progression in the field of biochemistry and data science, it will not be long before we witness the widespread application of CRISPR/Cas9 in the field of cancer therapeutics and research. Finally, a list of clinical trials applying CRISPR/Cas9 has been provided in the final section of this paper.