Prostate cancer amino acid metabolism resistance study

Weill Cornell Medicine investigators published a preclinical study in Nature Metabolism on August 20, 2026, revealing that prostate cancer cells can rewire amino acid metabolism to override normal cholesterol production controls, potentially fueling hormone therapy resistance. The study found that propionyl-CoA, produced from the breakdown of isoleucine and valine, stabilizes the protein SREBP2 via propionylation, keeping cholesterol-producing genes active. This allows cancer cells to produce androgens and maintain androgen receptor signaling, reducing responsiveness to drugs like enzalutamide. In mouse models, restricting isoleucine and valine slowed tumor growth and reduced lung metastases, while boosting propionyl-CoA had the opposite effect. The findings suggest potential new drug targets and dietary strategies, and may help explain why statins benefit some prostate cancer patients. The research was supported by the United States — National Institutes of Health. Senior author John Blenis and lead author Zhongchi Li are founders and equity holders of Elikia Inc., which targets aging-related metabolic dysfunction.