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2020 Rob & Cindy Citrone-PCF Young Investigator Award

Discovering Precision Oncology Approaches for CDK12-Deficient Prostate Cancer

Jonathan Chou, MD, PhD

University of California, San Francisco

Mentors: Alan Ashworth, PhD; Felix Feng, MD

Description:

  • Metastatic castration-resistant prostate cancer (mCRPC) is an incurable and invariably fatal disease, and new precision medicines are urgently needed.
  • Studies have found that mCRPCis comprised of distinct molecular subtypes with differing biology, treatment responses, and clinical outcomes. One of the most recent subtypes identified is characterized by mutations in both copies of the CDK12 gene.
  • CDK12-mutated prostate cancers have features of more aggressive disease, including higher Gleason score, and shorter time to developing resistance to hormonal therapies, compared to other subtypes.
  • Dr. Jonathan Chou is studying the biology of CDK12-mutated prostate cancers, in order to identify new therapeutic strategies for this molecular subtype of prostate cancer.
  • Dr. Chou will evaluate whether CDK12-loss alters the activity of the androgen receptor (AR), which is the primary driver of prostate cancer and the target of hormonal therapy.
  • Whether targeting other related CDK genes can specifically kill tumor cells with CDK12 mutations will be tested.
  • In addition whole genome CRISPR (gene knockout) screens will be conducted to identify any other proteins in the human genome that may be promising therapeutic targets in CDK12-mutated prostate cancer.

What this means to patients: Dr. Chou is studying the biology of CDK12-mutatedprostate cancers, a distinct molecular subtype of prostate cancer, which is seen in~7% of mCRPC patients. This project will identify the impact of CDK12 mutations on the AR pathway, and identify new treatment targets for patients with this morea ggressive subtype of prostate cancer.