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Amino acid metabolism rewiring leads to hormone therapy resistance in prostate cancer

Prostate tumors can rewire amino acid metabolism to override the normal brakes on cholesterol production, a process that may fuel hormone therapy resistance, according to a new study.

The preclinical study, published in Nature Metabolism, revealed that a compound called propionyl-CoA, produced by the breakdown of amino acids isoleucine and valine during normal energy metabolism, acts as a signal that switches on cholesterol production. This helps prostate cancer cells adapt to the hormone-deprived conditions resulting from treatment and acquire more aggressive features.

By revealing this previously unrecognized connection, the study identified a potential weakness in prostate cancer that could be targeted with new drugs or, pending clinical testing, dietary strategies that reduce levels of isoleucine and valine. These essential amino acids are abundant in protein-rich foods such as meat, fish and dairy products.

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