AI Article Synopsis
- This study investigates how the metabolism of acetate influences neurodifferentiation and contributes to castration-resistant prostate cancer (CRPC) that resists hormone therapy.
- Researchers used advanced techniques to analyze prostate cancer tissues and developed various models to understand the mechanism behind this metabolic change.
- The results indicate that inhibiting a specific enzyme, ACSS2, alongside traditional hormone therapy, could potentially reduce tumor size and offers a new, less toxic treatment approach for patients with this aggressive cancer subtype.
Article Abstract
Aims: Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC).
Methods: We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies.
Results: The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume.
Conclusion: Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.
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| http://dx.doi.org/10.1016/j.drup.2024.101158 | DOI Listing |
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