缓慢循环的LGR5瘤群体在治疗后调解基底细胞癌复发
Adriana Sánchez-Danés1, Jean-Christophe Larsimont1, Mélanie Liagre1
1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium.
Nature
|October 10, 2018
概括
通过促进瘤细胞分化来治疗基底细胞癌 (BCC). 将这种Smoothened抑制剂与Wnt途径阻断剂相结合,可以消除持久性BCC细胞,防止复发.
科学领域:
- 癌症学
- 皮肤病学
- 分子生物学
背景情况:
- 基底细胞癌 (BCC) 是最常见的人类癌症,由异常的刺道信号驱动.
- 像vismodegib这样的平滑抑制剂用于介导癌症,但它们在BCC回归和复发中的确切机制尚不清楚.
研究的目的:
- 阐明Smoothened抑制导致BCC瘤回归的机制.
- 在vismodegib治疗后确定瘤复发的细胞基础,并探索根除策略.
主要方法:
- 使用两个基因工程小鼠模型的基底细胞癌.
- 研究了vismodegib对瘤细胞分化的影响,并确定了持久性细胞群.
- 分析了小鼠和人类BCC样本中的LGR5表达和Wnt信号活动.
主要成果:
- 通过抑制毛囊分化和促进瘤细胞分化来调解BCC回归.
- 缓慢循环的LGR5表达瘤细胞的子群持续存在,导致复发.
- 在小鼠模型中,使用vismodegib和Lgr5线系切除或Wnt抑制的联合治疗消除了BCC.
结论:
- 通过促进瘤细胞分化诱导BCC回归.
- 针对持久的LGR5阳性,Wnt活跃的瘤细胞对于预防复发至关重要.
- 结合Smoothened和Wnt途径抑制剂是克服BCC复发的有希望的临床策略.
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