抗酶胺耐药的STEAP4+ MyoCAF分泌酸胆,通过激活激素敏感前列腺癌的干细胞来促进进展
Wenhao Wang1, Jing Zhao1, Tiewen Li1
1Department of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 8, 2025
概括
前列腺癌中的恩扎胺耐药性涉及 STEAP4+ 肌纤维细胞癌相关的纤维细胞,激活自和脂质生产. 这创造了一个促进瘤的微环境,推动治疗逃脱和抗雄激素治疗的抗性.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 分子医学是分子医学.
背景情况:
- 对恩扎胺 (ENZ) 的治疗耐药性仍然是治疗晚期前列腺癌的重大挑战,导致割耐性前列腺癌 (CRPC).
- 了解驱动ENZ耐药性的机制对于开发有效的治疗策略至关重要.
研究的目的:
- 确定新的细胞机制和途径,有助于前列腺癌中的恩扎胺耐药性.
- 阐明癌症相关纤维细胞在调解治疗耐药性的作用.
主要方法:
- 对激素敏感前列腺癌 (HSPC) 和ENZ治疗的瘤进行全面的单细胞转录基因分析.
- 综合性脂质和功能分析,以调查分子途径.
- 对转录因子结合和信号轴激活的分析.
主要成果:
- 确定了与不良临床结果和ENZ耐药性相关的STEAP4+肌纤维细胞癌相关纤维细胞 (myoCAFs) 的扩张.
- 发现了一种新的途径,即STEAP4+肌细胞中TFE3转录因子的激活可以通过PCYT1A驱动自和酸丁胆的过度生产.
- 证明这种富含脂的微环境激活了癌细胞中的HSP90/HIF1A信号,促进了干细胞和治疗逃逸.
结论:
- STEAP4+ myoCAF-TFE3/瘤-HIF1A轴是前列腺癌中抗雄激素抵抗的关键调节器.
- 针对这一轴提出了一个有前途的治疗策略,以克服恩扎拉胺耐药性,并提高晚期前列腺癌的治疗疗效.
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