Dr. Bryce on Ongoing Research Regarding CDK12 Alterations in Prostate Cancer

Alan H. Bryce, MD, assistant professor of medicine and medical director of the Genomic Oncology Clinic, Mayo Clinic, discusses ongoing research regarding CDK12 alterations in prostate cancer.

CDK12-altered prostate cancer accounts for 5% to 10% of all prostate cancers, says Bryce. Patients with a CDK12 mutation have a poor response to traditional antiandrogen agents such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi), and PARP inhibitors. However, these patients appear to respond well to immunotherapy.

CDK12 appears to regulate chromosomal stability, says Bryce. As such, a CDK12 mutation can lead to large tandem duplications and chromosomal rearrangements, which increases neoantigen production.

In a retrospective, multicenter analysis of 58 men with monoallelic CDK12 alterations, 8 patients with metastatic castration-resistant prostate cancer had been treated with a PD-1 inhibitor. Among these patients, 38% had a prostate specific antigen₅₀ (PSA₅₀) response, explains Bryce. Additionally, none of the 11 patients treated with a PARP inhibitor had a PSA₅₀ response.

With further research, CDK12 could become a biomarker of response to checkpoint inhibitors in prostate cancer, concludes Bryce.