Synthetic Lethal Targeting of Cyclin Dependent Kinase-12-Deficient Prostate Cancer with PARP Inhibitors

Using isogenic prostate cancer models generated by CRISPR/Cas9-mediated inactivation of CDK12, the authors conducted a chemical library screen of ~1800 FDA-approved drugs. They inhibited cyclin K and CDK13 and evaluated the effects on poly ADP-ribose polymerase inhibitor (PARPi) sensitivity.