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2021 PCF Young Investigator Award

Understanding PSMA Expression Through a Deep Dive into the Genetic, Gene Expression and Microenvironment Profiles of mCRPC

Anna Trigos, PhD
Peter MacCallum Cancer Centre

Mentors: Shahneen Sandhu, MBBS, Michael Hofman, MBBS, David Quigley, PhD

Description:

  • 177Lu-PSMA-targeted radionuclide therapy (LuPSMA) is a new PSMA-targeted treatment for prostate cancer, poised to become a new standard of care.
  • However, a third of men with metastatic castration resistant prostate cancer (mCRPC) have limited responses to LuPSMA treatment, and all patients who initially respond eventually develop progressive disease.
  • Unfortunately, our understandings of the function of PSMA in prostate cancer, what governs PSMA expression, and mechanisms of resistance to LuPSMA are limited.
  • Dr. Anna Trigos is studying the molecular factors associated with various patterns of PSMA expression and LuPMSA responses in prostate cancer patients.
  • In this project, Dr. Trigos will perform comprehensive molecular profiling on tumor samples from mCRPC patients who have undergone PSMA-PET scans and/or LuPSMA treatment, to identify genetic alterations, gene expression profiles and tumor microenvironment patterns that associate with various patterns of PSMA expression, in LuPSMA-naïve and LuPSMA-resistant disease.
  • If successful, this project will identify molecular factors associated with distinct PSMA expression patterns and clinical phenotypes, and molecular changes associated with acquired resistance to LuPSMA. This will help narrow down potential combination therapies for LuPSMA and refine biomarkers for patient selection.

What this means to patients: LuPSMA is a promising new treatment that will likely soon become approved for patients with metastatic castration resistant prostate cancer (mCRPC). However, PSMA, the target of the treatment, is not uniformly expressed on all prostate cancer cells, and it is unclear how this and other factors influence responses to LuPSMA. Dr. Trigos will create a profile of molecular features that associate with PSMA expression patterns and response and resistance to LuPSMA. This will enable identification of potential treatment approaches to improve the efficacy of LuPSMA.