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Updated: Jun 10, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Acetate utilization promotes hormone therapy resistance in prostate cancer through neuroendocrine differentiation
Dajun Gao1, Yanting Shen2, Lingfan Xu3
1Department of Urology, Shanghai Ninth People's Hospital, Shanghai, China.
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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12:13Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
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