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2020 Peter & Laurie Grauer-PCF Young Investigator Award

Using CDK4/6 Inhibition to Augment PSMA Expression in Advanced Prostate Cancer and Enhance Clinical Responses to PSMA-Targeted Radioligand Therapy

Vadim Koshkin, MD

University of California, San Francisco

Mentors: Eric Small, MD; Thomas Hope, MD; Luke Gilbert, PhD

Description:

  • Prostate-specific membrane antigen (PSMA) is a protein that is commonly present at high levels on prostate cancer cells but is low or absent on normal tissue, and is a promising new target for anti-cancer treatments.
  • The PSMA-targeted radioligand therapy,177Lu-PSMA-617, is a new PSMA-targeting therapy that delivers cancer-killing radiation to prostate cancercells.177Lu-PSMA-617 is currently being tested in phase III clinical trials in metastatic castration resistant prostate cancer (mCRPC).
  • Dr. Vadim Koshkin had found that downregulation of CDK4 can increase PSMA levels on prostate cancer cells, and is investigating whether CDK4/6-targetingtreatments can improve the efficacy of177Lu-PSMA-617.
  • In this project, Dr. Koshkin will test the effects of CDK4/6-inhibitors on PSMA levels in pre-clinical prostate cancer models, and use this information to design clinical trials testing CDK4/6-inhibitors +177Lu-PSMA-617.
  • Dr. Koshkin will then conduct a clinical trial to assess the impact of treatment with a CDK4/6-inhibitor on PSMA expression on prostate tumors, and the safety and efficacy of treatment with the CDK4/6-inhibitor followed by177Lu-PSMA-617.
  • If successful, this project will result in a highly promising new treatment strategy for patients with advanced prostate cancer.

What this means to patients: Dr. Koshkin will test the efficacy of a novel treatment strategy that uses a CDK4/6-inhibitor followed by PSMA-targeted radioligand therapy in patients with mCRPC, which may improve outcomes and treatment options in patients with advanced prostate cancer.