乙酸的利用通过神经内分泌分化促进前列腺癌的激素治疗耐药性
Dajun Gao1, Yanting Shen2, Lingfan Xu3
1Department of Urology, Shanghai Ninth People's Hospital, Shanghai, China.
乙酸的代谢推动了割抵抗性前列腺癌 (CRPC) 中的神经差异化. 用抑制剂向乙-A合成酶短链家族成员2 (ACSS2) 为CRPC提供了一个有前途的治疗策略.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 癌症生物学 癌症生物学
背景情况:
- 瘤脂肪酸代谢可塑性有助于癌症的治疗耐药性.
- 神经差异化 (NED) 与割抵抗性前列腺癌 (CRPC) 的进展有关.
研究的目的:
- 调查乙酸代谢在NED介导的CRPC中的作用.
- 为了确定CRPC的潜在治疗点.
主要方法:
- 临床前列腺癌组织的液体染色学-并联质谱学 (LC-MS/MS) 分析.
- 建立瘤异种移植小鼠模型,原发性瘤细胞和人类衍生器官.
主要成果:
- 激素治疗通过短链乙-CoA合成酶家族成员2 (ACSS2) 上调了酸盐代谢.
- ACSS2增加了c-MYC表达,诱导了NED.
- 结合ACSS2抑制剂和胺胺治疗减少了异体移植中的瘤体积.
结论:
- 在NED介导的CRPC中,乙酸盐代谢至关重要.
- 与激素治疗相结合的ACSS2抑制剂为CRPC提供了一种新的低毒性治疗策略.
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