Project Title: Targeting Lipid Metabolism and Diet in Patients with Locally Advanced Prostate Cancer

Principal Investigator: Massimo Loda, MD (Weill Cornell Medicine)

Co-Investigators: David Nanus, MD (Weill Cornell Medicine), Christopher Barbieri, MD, PhD (Weill Cornell Medicine), Caroline Ribeiro, PhD, MSc (Weill Cornell Medicine), Marcus DaSilva Goncalves, MD, PhD (Weill Cornell), Katie Hootman, PhD (Weill Cornell Medicine), James Kelly, PhD (Weill Cornell Medicine), Karla Ballman, PhD, MS (Weill Cornell Medicine), Pier Vitale Nuzzo, MD, PhD (Weill Cornell Medicine), Steve Plymate, MD (University of Washington) Johan Swinnen, PhD (International Food Policy Research Institute)

Description:

• A hallmark of cancer cells is altered cellular metabolism, to support their constant and rapid growth. In contrast to normal cells, which take up nutrients from their environment according to their needs, prostate cancer cells fuel themselves by synthesizing large amounts of lipids.
• FASN is an enzyme critical for lipid generation in prostate cancer cells. Previous preclinical studies have demonstrated that targeting FASN suppresses prostate tumor growth. This suggests that FASN-inhibitors may be promising treatments for prostate cancer.
• Further, Dr. Loda and colleagues hypothesize that dietary modulation of the exogenous lipids used in lipid synthesis pathways can potentiate the efficacy of FASN-inhibitors.
• In this project, Dr. Loda and team are conducting a phase 2 clinical trial to evaluate the efficacy of a FASN inhibitor plus a custom and metabolically defined PUFA-rich, limited-fat diet in patients newly diagnosed with locally advanced prostate cancer who plan to undergo subsequent radical prostatectomy.
• Whether molecular imaging and metabolic/lipid profiling may function as biomarkers to monitor patient responses to the FASN-inhibition + a PUFA-rich diet intervention, will be investigated.
• In parallel, preclinical studies will be conducted to evaluate the mechanisms by which PUFAs enhance the efficacy of pharmacologic FASN inhibition.
• If successful, this project will result in a new therapeutic approach combining diet and pharmacologic intervention of a critical metabolic vulnerability in prostate cancer, and will determine the mechanisms of action of this treatment.

What this means to patients:  Altered metabolism is a hallmark of cancer but may also represent a vulnerability that can be therapeutically targeted.  Prostate cancer fuels itself through synthesizing its own lipids using the enzyme FASN.  Dr. Loda and team are conducting a clinical trial to test the effects of combining a treatment targeting FASN with a diet that modulates the levels of dietary lipids used in lipid synthesis pathways.  This may ultimately lead to a new treatment for prostate cancer patients, insights into the mechanisms of action, and biomarkers to guide management of patients considering or undergoing this treatment.