Asian Oncology Research Journal

Clustered regularly interspaced short palindromic repeats (CRISPR) technologies have been described as precision instruments capable of countering the evolutionary adaptability that underlies treatment failure in cancer. The evidence supporting that description is uneven. This critical narrative review examines how CRISPR-based editing contributes to three distinct problems in oncology: the discovery of genetic dependencies and resistance mechanisms, the measurement of clonal and phenotypic dynamics within tumours, and direct therapeutic intervention. Literature was identified through structured searching of biomedical and multidisciplinary scholarly sources, complemented by backward and forward citation searching, with bibliographic details and digital object identifiers verified against registry and publisher records. Evidence was appraised for design adequacy, contextual realism, replication and translational relevance rather than aggregated quantitatively.

Three conclusions emerge with differing degrees of confidence. Pooled and variant-resolution editing screens have reliably and reproducibly identified context-specific vulnerabilities, and the principal methodological weakness is no longer library design but the artificiality of the systems in which screens are performed. Lineage-recording systems have converted tumour evolution from an inference drawn from static sequencing snapshots into a directly observable process, yet nearly all such evidence derives from engineered murine or xenograft settings, and the transfer of these observations to spontaneous human disease remains unproven. Therapeutically, the strongest clinical evidence concerns ex vivo multiplex editing of immune effector cells, where early-phase trials demonstrate feasibility and acceptable short-term safety but limited and inconsistent efficacy in solid tumours; direct in vivo editing of malignant cells remains preclinical, constrained by delivery rather than by editing chemistry.

A persistent contradiction runs through the field: the same double-strand break activity that enables editing imposes selective pressure favouring cells with impaired p53 signalling and can generate large-scale structural rearrangement, so the intervention intended to constrain tumour evolution may itself act as an evolutionary force. Resolving this tension, and testing whether editing-derived insight can be converted into durable evolutionary control rather than transient response, represents the central unmet requirement of the field.