Use of CRISPR-Cas9 in oncology: systematic review of preclinical in vivo studies and phase I clinical trials

Abstract

The use of CRISPR-Cas9-based therapies for cancer has been proposed as promising; however, clinical evidence remains limited and heterogeneous. We conducted a systematic review of preclinical in vivo studies and clinical trials to synthesize the evidence on the efficacy and safety of CRISPR-Cas9 therapeutic interventions in oncology. We searched the MEDLINE/PubMed and EBSCO databases up to July 8, 2025. We included studies (2019–2024) in English or Portuguese involving humans or in vivo animal models with cancer that used CRISPR-Cas9 as a therapeutic intervention; we excluded in vitro-only studies, non-oncological applications, theoretical proposals, reviews, and duplicates. Due to heterogeneity, we employed narrative synthesis; risk of bias was assessed using ROBINS-I (clinical trials) and SYRCLE (preclinical), and the certainty of evidence was judged using GRADE.

We identified 10 eligible studies (5 phase I clinical trials; 5 preclinical in vivo studies). In the clinical trials (n=36), interventions were mostly PD-1 deletion in T cells (e.g., editing via electroporation), with outcomes showing partial responses ranging from 0–19% and stable disease in up to 47% of patients; one study reported a median survival of 42.6 weeks. Reported toxicity was generally low to moderate; chromosomal translocations were observed in one study. In preclinical models, significant tumor suppression was observed in all studies, with average reductions of ~50–70% in tumor volume/metastases compared to controls (p<0.05 in most), and low apparent toxicity. The overall certainty of the evidence was very low for both efficacy and safety, mainly due to high/moderate risk of bias, small sample sizes, inconsistency, and imprecision.

This review indicates that CRISPR-Cas9-based oncological therapies show initial signs of safety and biological activity, but current evidence is insufficient to establish superiority over conventional treatments. Phase II/III controlled trials with larger sample sizes, standardized outcomes, and long-term monitoring (including off-target effects) are required before any widespread clinical adoption.