Functional Genomic Analysis of CDK4 and CDK6 Gene Dependency across Human Cancer Cell Lines.

ABSTRACT: Cyclin-dependent kinase 4 (CDK4) and CDK6 are key cell-cycle regulators that are frequently dysregulated in human malignancies. CDK4/6 inhibitors are clinically approved for the treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, but improved specificity and reduced toxicity might expand their use to other indications. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, we found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. CDK6 expression was the best single predictor of CDK4 (negatively correlated) and CDK6 (positively correlated) dependencies in the cancer cell lines, with adeno

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC9618034 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature