A Mayo Clinic study demonstrated how the deficiency of the enzyme CDK12 or its regulation by cyclin K causes the expression of mutations related to resistance to endocrine therapy in prostate cancer. Prostate tumors with CDK12 deficiency are more aggressive, recurrent, produce metastases and are associated with castration-resistant prostate cancer (CRPC). CDK12 deficiency impairs DNA repair and increases genomic instability, causing an effect known as homologous recombination deficiency or BRCAness.