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2025 Republic National Distributing Company-PCF Challenge Award

Elucidating New Molecular Targets and Defining the Androgen Spatial Heterogeneity in Lethal Prostate Cancer

Principal Investigator: Nima Sharifi, MD (University of Miami)

Co-Investigators: Mary-Ellen Taplin, MD (Harvard: Dana-Farber Cancer Institute (DFCI), Sanoj Punnen, MD (University of Miami), Brandon Mahal, MD (University of Miami)

Young Investigator: Pedro Freitas, MD (University of Miami)

Description:

  • Androgen deprivation therapy (ADT) is a major part of the treatment for advanced prostate cancer. The importance of androgens produced by the testes has been known for over 80 years and the past 15 years has brought advancement with therapies that block androgens made by other organs, namely the adrenal glands. However, blocking both testicular and adrenal androgens together still leaves residual androgens that can drive therapy resistance, as current anti-androgen therapies such as abiraterone are unable to block these alternative androgen production pathways. It is critical to determine the source of these alternate androgens, often produced within prostate tumors, to develop better treatments for prostate cancer.
  • In this project, Dr. Nima Sharifi and team are mapping a completely new pathway of androgen production and will identify the enzymes responsible as well as new targets for drug therapy. They will also determine the identity of the cells that make these residual androgens by spatially mapping out where they are located in tumors.
  • If successful, this project will lead to the development of new drug targets and drugs, as well as development of biomarkers to determine how an individual should be treated based on how their tumor makes androgens.

What this means to patients: Anti-androgen therapies are the backbone of treatment for aggressive and advanced prostate cancer, and target the metabolic pathways known to produce androgens; however alternate pathways continue to produce residual androgens and contribute to treatment resistance and disease progression. Dr. Sharifi and team’s project will map the cells and molecular pathways responsible for generating alternative androgens, and will identify targetable vulnerabilities. This will guide development of novel hormonal therapies for prostate cancer and ultimately improve patient outcomes.