Functional redundancy between atypical CDKs reveals a vulnerability in hepatocellular carcinoma.

Concomitant inactivation of CDK16 and CDK18 in liver cancer cells causes persistent DNA repair defects and cell death, linked to nucleocytoplasmic transport control via nuclear pore phosphorylation.

• Why it matters: Individual depletion of atypical CDKs (CDK14–18) has not shown sustained therapeutic relevance, leaving a vulnerability in liver cancer unclear.
• What they did: The study shows CDK16 and CDK18 compensate each other, and that genetic ablation of Cdk16 and Cdk18 in established MYC- and beta-catenin-driven liver tumors triggers DNA damage.
• The result: Tumor regression follows DNA damage in cancer cells without affecting adjacent normal tissue, supporting CDK16–18 inhibitor development for aggressive hepatocellular carcinoma.