Whereas disruption of these CDK12 regulatory networks likely contributes to the origin of tandem DNA duplications that are a hallmark of genomic instability in cancers with biallelic CDK12 inactivation (23,25,26), the requirement for HR gene expression has invigorated efforts for therapeutic targeting of CDK12, particularly in combination with PARP inhibitors that are effective in HR-deficient cancer cells (27–29). This evidence concerns the gene CDK12 and cancer.