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2025 Ben Schenkman – PCF Young Investigator Award

Lipid Metabolism as a Key Regulator of Prostate Cancer State Transitions and Therapy Resistance

Silvia Rodrigues, PhD
Weill Cornell Medicine 

Mentors: Max Loda; David Goodrich

Description:

  • Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but resistance leads to castration-resistant prostate cancer (CRPC) which may transition into an aggressive androgen-independent subtype called neuroendocrine prostate cancer (NEPC). 
  • Metabolic alterations, particularly altered lipid metabolism, is an underexplored driver of prostate cancer disease progression and therapy resistance. Fatty acid synthase (FAS), a key enzyme in lipid metabolism, is increased in advanced prostate cancer and contributes to tumor adaptation under therapeutic stress, suggesting its potential as a therapeutic target. 
  • Dr. Silvia Rodrigues aims to determine the role of lipid metabolism, specifically FAS, in driving PC state transitions and therapy resistance. 
  • In this project, Dr. Rodrigues will define how FAS-driven lipid metabolism promotes tumor plasticity, therapy resistance, and NEPC emergence, and investigate how dietary fatty acids influence tumor metabolism, plasticity, and therapeutic outcomes. These studies will clarify the metabolic mechanisms underlying prostate cancer progression and identify potential therapeutic and dietary interventions.
  • If successful, this study will define the biological relationships between lipid metabolism, AR signaling, and lineage plasticity, highlighting the therapeutic implications of metabolic interventions in overcoming therapy resistance by applying of dietary strategies and pharmacologic interventions for prostate cancer management.

What this means to patients: Metabolic alterations are emerging as a key driver of prostate cancer progression and treatment resistance. Dr. Rodrigues’ project will determine how lipid metabolism modulates prostate cancer state transitions and therapy resistance, and define the biologic impacts and therapeutic potential of FAS inhibition and dietary lipid composition. These findings will inform novel therapeutic strategies combining metabolic inhibitors and AR inhibitors, optimize dietary interventions for prostate cancer management, and contribute to precision medicine approaches for treatment-resistant prostate cancer.