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2022 Point Biopharma – PCF Young VAlor Investigator Award

Elucidating Molecular Correlates of PSMA Expression in Prostate Cancer Liquid Biopsies to Identify Biomarkers of Response and Resistance to PSMA-Targeted Therapies

Marina Sharifi, MD, PhD
University of Wisconsin

Mentors: Joshua Lang, MD, Shuang Zhao, MD, MSc, Brett Carver, MD

Description:

  • The PI3K pathway is the most commonly mutated tumor-driving pathway in prostate cancer, with mutations occurring in more than 50% of mCRPC. However, clinical efficacy of PI3K pathway inhibitors has been modest, even in patients with PI3K pathway-mutated prostate cancer.
  • Early data suggest the newly approved treatment LuPSMA may synergize with PI3K pathway-targeting treatments. LuPSMA is a molecular radiotherapy that targets the prostate cancer-associated protein PSMA.
  • Dr. Sharifi’s project will define the mechanisms by which synergy between LuPSMA or PI3K pathway inhibitors may occur.
  • Whether and how PI3K pathway mutations affect PI3K pathway activity and PSMA levels will be investigated.
  • Circulating tumor cells from patients on clinical trials will be studied to determine whether they may be useful liquid biopsy biomarkers for determining PI3K pathway status in patients.
  • If successful, this project will define the biology of how the PI3K and PSMA pathways intersect, and provide rationale for a precision medicine clinical trial testing the combination of PI3K-inhibitors and LuPSMA.

What this means to patients: LuPSMA is a promising new treatment for mCRPC, yet patients eventually experience disease recurrence and progression, thus additional optimization is needed. Dr. Sharifi and colleagues will investigate mechanisms of synergy between LuPSMA and PI3K pathway inhibitors and develop liquid biopsy tests that can be used as biomarkers for selecting patients who may benefit from this combination treatment. This may lead to new clinical trials testing this approach in patients.