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2021 Art Kern in Honor of Plum and Jonathan W. Simons, MD-PCF Young Investigator Award

Therapeutic Implications of Low PSMA PET Uptake in Castration-Resistant Prostate Cancer

Ivan de Kouchkovsky, MD
University of California, San Francisco

Mentor: Rahul Aggarwal, MD

Description:

  • Prostate specific membrane antigen (PSMA) is a protein present on the surface of most prostate cancer cells, and a target of new PET imaging agents and therapies. PSMA is biologically linked to AR, the target of standard prostate cancer hormonal therapies. However, some patients have low PSMA levels on their tumors, and these tumors are often more aggressive and less responsive to prostate cancer therapies.
  • Dr. Ivan de Kouchkovsky is studying the biology and clinical significance of PSMA-low prostate cancer.
  • In this project, Dr. de Kouchkovsky will compare the efficacy of AR-targeted therapy in metastatic castration resistant prostate cancer (mCRPC) patients with low versus high PSMA levels on PSMA PET imaging.
  • Metastatic tumor biopsies collected from patients before treatment will be studied to identify key molecular features that differ between PSMA-low vs. PSMA-high tumors.
  • The expression of two possible new therapeutic targets, CD46 and CDCP1, in PSMA-low tumors will be evaluated, to determine if these may represent promising new treatment targets in these tumors.
  • If successful, this project will identify clinical and molecular differences between PSMA-low vs. PSMA-high tumors and identify possible new treatment options for PSMA-low prostate cancer.

What this means to patients: PSMA-low prostate tumors are present in a subset of mCRPC patients, and are often more aggressive. Dr. de Kouchkovsky will determine if these tumors are less responsive to standard hormonal therapies and identify molecular differences that may lead to the establishment of new treatment approaches. These results will have direct implications for the management of mCRPC patients with PSMA-low PSMA tumors help guide treatment decisions in this patient population.