在前列腺癌中CAF可塑性和抗性的关键相互作用
Xiaoling Li1, Ping Mu1,2,3
1Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas.
Cancer research
|July 28, 2023
概括
抗雄激素剥夺疗法可以诱导与癌症相关的纤维细胞,促进割抵抗性前列腺癌 (CRPC) 的发展. 向这些纤维细胞可能提供克服CRPC和治疗耐药性的新策略.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
背景情况:
- 前列腺癌 (PC) 是由雄激素受体 (AR) 途径驱动的,雄激素剥夺疗法 (ADT) 是标准治疗方法.
- 割耐药前列腺癌 (CRPC) 的发展,以增加瘤异质性和可塑性为特征, presents一个显著的临床挑战.
- 与内在瘤机制相比,瘤微环境在PC复发和药物耐药性中的作用尚未得到充分探索.
研究的目的:
- 研究瘤微环境,特别是癌症相关纤维细胞 (CAFs) 在CRPC发展中的作用.
- 了解ADT如何影响CAF表型,并有助于CRPC进展.
- 为了确定CRPC治疗的 stromal区内潜在的治疗点.
主要方法:
- 利用各种阶段的前列腺瘤的基因工程小鼠模型 (GEMMs).
- 使用单细胞RNA测序 (scRNA-seq) 来分析细胞组成和基因表达.
- 专注于识别特定的纤维细胞亚型及其在瘤微环境中的相互作用.
主要成果:
- 在前列腺瘤中,ADT诱导SPP1+肌纤维细胞癌相关纤维细胞 (myCAFs).
- 这些治疗诱导的myCAFs在CRPC的发展和进展中发挥着关键作用.
- 证明了ADT诱导的CAF表型变化和疾病进展之间的相关性.
结论:
- 在ADT后,SPP1+ myCAFs是CRPC发育的关键媒介.
- 治疗引起的CAF变化与前列腺癌的进展和治疗耐药性有关.
- 向体区,特别是myCAFs,是对抗CRPC的有希望的治疗策略.
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