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2024 Jenny Johnson Family Foundation – PCF Young Investigator Award

Metabolic Targeting of Poor Prognostic Prostate Cancer

Tahlia Scheinberg, MBBS
Chris O’Brien Lifehouse

Mentors: Lisa Horvath, MBBS, PhD; Lisa Butler, PhD; David Labbé, PhD

Description:

  • Despite recent advances in the treatment of advanced prostate cancer, therapeutic resistance remains the key cause of lethal disease. Novel treatment strategies are urgently needed. 
  • One promising area is the metabolic environment that affects growth, progression, and therapeutic resistance in prostate cancer.
  • Dr. Tahlia Scheinberg and team has previously validated a plasma lipidomic biomarker enriched with ceramides, PCPro, as capable of prospectively identifying patients with poor prognosis metastatic castration resistant prostate cancer (mCRPC). 
  • In this project, the ability of the PCPro biomarker to predict patient outcomes will be further validated in additional patient cohorts, including clinical trials testing PSMA-targeted radioligand therapy in patients with mCRPC, and trials testing various therapies in earlier disease settings.
  • Novel therapies targeting sphingolipid metabolism will be tested as monotherapies and in combination with androgen-targeted therapies in preclinical models. The effect of these treatments on lipid metabolism in the tumor and circulation will also be assessed.
  • If successful, this project will further validate a lipid-based prognostic biomarkers for patients with poor prognostic prostate cancer and identify novel lipid-targeted therapies that have potential to overcome AR-therapy resistance.

What this means to patients: A hallmark of tumor biology is altered metabolism, which is being studied for its potential as a biomarker of patient outcomes and therapeutic vulnerability. Dr. Scheinberg’s project will validate a lipid-based biomarker for the potential to predict patients outcomes across the disease spectrum and during treatment with various standard therapies, and determine the potential for a sphingolipid metabolism-targeting drug as a new therapeutic strategy for prostate cancer. This program addresses the key issue of overcoming drug resistance in prostate cancer through precision metabolic therapy, to improve the length and quality of life of patients with prostate cancer.