Analysis by Broad Institute researchers revealed that CRISPR-Cas9 guide RNAs used in large-scale genome-wide cancer dependency screens perform unevenly across cell lines derived from different ancestries. Approximately 2.17% off-target rates were observed in African ancestry cell lines compared to 1.78% in others. This disparity could lead to missed identification of critical cancer vulnerabilities in understudied populations. The findings highlight the importance of considering genetic diversity in CRISPR guide design to enhance equitable translational cancer research.