针对黑色素瘤的最小残留病导治疗
Florian Rambow1, Aljosja Rogiers1, Oskar Marin-Bejar1
1Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, KU Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
Cell
|July 19, 2018
概括
晚期癌症的最小残留疾病 (MRD) 可能导致复发. 在RXRG的推动下,针对MRD的神经干细胞 (NCSC) 程序提供了一种克服黑色素瘤治疗阻力的新策略.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 晚期的癌症通常会获得初始的治疗反应,但会保持最小的残留疾病 (MRD),导致复发.
- 了解MRD背后的生物机制对于开发有效的治疗策略至关重要.
- 由于它们对向治疗的反应,BRAF突变黑色素瘤是癌症研究的重要焦点.
研究的目的:
- 研究BRAF突变黑色素瘤中最小残留疾病 (MRD) 的生物特征.
- 在RAF/MEK抑制后在MRD中识别耐药转录状态.
- 探索特定的转录程序及其驱动器在治疗耐药性的作用.
主要方法:
- 单细胞RNA测序用于来自患者的异种移植 (PDX) 黑色素瘤模型中的恶性细胞.
- 这些模型同时接受RAF/ MEK抑制剂的治疗.
- 从PDX和患者活检中分析了MRD中的转录状态.
主要成果:
- 在MRD中发现了不同的药物耐受性转录状态.
- 在MRD中发现了一个由核受体RXRG驱动的神经干细胞 (NCSC) 转录程序.
- 抑制RXR (视网膜X受体) 减少了MRD中NCSC的积累,并延迟了耐药性的发展.
结论:
- 神经干细胞 (NCSC) 被确定为最小残留疾病 (MRD) 治疗耐药性的关键驱动因素.
- 针对RXRG和NCSC方案是针对MRD治疗的潜在治疗策略.
- 可以利用重编程基因调节网络架构来限制细胞异质性并克服抗性.
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