雄激素受体阻塞促进对BRAF/MEK向治疗的反应
Christopher P Vellano1, Michael G White2, Miles C Andrews2,3
1TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nature
|June 15, 2022
概括
与男性相比,女性黑色素瘤患者对BRAF/ MEK向治疗的反应显著改善. 针对雄激素受体通路可以提高两性治疗的疗效.
科学领域:
- 癌症学
- 癌症研究
- 药理学
背景情况:
- 针对BRAF/MEK的治疗已经改变了癌症治疗,但仍面临治疗耐药性的挑战.
- 了解影响治疗反应的因素对于开发创新策略至关重要.
研究的目的:
- 研究男性和女性黑色素瘤患者对BRAF/ MEK向治疗的反应差异.
- 探索雄激素受体通路在治疗反应和耐药性的作用.
主要方法:
- 对接受新辅助和转移性BRAF/MEK向治疗的患者队列的分析.
- 在小鼠模型中进行临床前研究,以评估抗瘤活性和雄激素受体信号的影响.
- 药物抑制和诱导雄激素受体信号,以评估对治疗反应的影响.
主要成果:
- 与男性患者相比,女性患者表现出明显更高的重大病理反应率和改善的无复发生存率.
- 临床前模型显示雄性小鼠的抗瘤活性受损,与较高的雄激素受体表达相关.
- 在雄性和雌性小鼠中,抑制雌激素受体信号增强了BRAF/ MEK治疗反应,而诱导则降低了反应.
结论:
- 在黑色素瘤中,针对BRAF/ MEK的治疗反应的性别差异很大.
- 在调节BRAF/ MEK抑制剂的有效性方面,雄激素受体通路起着至关重要的作用.
- 向雄激素受体通路是克服耐药性和改善所有患者的潜在策略.
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