> Our Work > The Work We Fund

2023 Michael & Lori Milken – PCF Young Investigator Award

Molecular Correlates with Prostate-Specific Membrane Antigen (PSMA) in Prostate Cancer

Adam Weiner, MD
University of California, Los Angeles (UCLA)

Mentors: Rob Reiter, Paul Boutros, Jeremie Calais

Description:

  • Prostate cancer is heterogeneous in both biology and clinical phenotypes. Since treatment options and efficacies vary from one patient to another, current efforts to better characterize prostate cancer have resulted in new imaging strategies including positron emission tomography (PET) based on the protein prostate-specific membrane antigen (PSMA).
  • While PSMA PET is expected to increase in use, PSMA expression can vary and no studies have evaluated cancer phenotypes for primary tumors detected or not detected by PSMA PET prior to treatment. Thus, there is an unmet need to correlate tumor biology with PSMA PET to optimize prostate cancer imaging and define individual treatment susceptibilities.
  • Weiner and team are assessing the molecular and clinical profiles of primary prostate cancer with high vs low/no PSMA expression to derive PSMA PET thresholds that may be biologically and clinically relevant and to improve understanding of the mechanisms underlying PSMA expression.
  • Gene expression analyses will be performed on primary prostate cancer samples to investigate the differences in molecular pathways in tumors with high vs low PSMA expression. Tumor samples from several clinical trials will be studied to investigate associations with various treatments for prostate cancer.
  • The associations between tumor histology, molecular profiles, and PSMA PET levels will be investigated to determine whether PSMA PET positive tumors differ in aggressiveness based on tumor histology and molecular profiles, that are suggestive of treatment susceptibilities. These relationships will then be studied prospectively in a clinical trial, in patients with a high suspicion for prostate cancer undergoing imaging PSMA PET prior to prostate biopsy.
  • If successful, this project will define and validate the molecular biology and clinical features of primary prostate cancer that is PSMA high vs low on PSMA PET imaging. This will help clinicians to better use PSMA PET imaging at the time of diagnosis to risk stratify patients and identify optimal treatment strategies.

What this means to patients: Prostate cancer is highly heterogeneous with variations in aggressiveness and treatment susceptibilities. These biological variations are likely somewhat reflected in differences in PSMA uptake on PET which is an increasingly used technology for staging and detecting prostate cancer. Dr. Weiner and team will define the biological differences associated with differences in PSMA PET levels, which will help augment individualized cancer care for many future patients.