治療後の基礎細胞癌の再発を媒介するLGR5腫瘍群
Adriana Sánchez-Danés1, Jean-Christophe Larsimont1, Mélanie Liagre1
1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium.
Nature
|October 10, 2018
まとめ
Vismodegibは,腫瘍細胞の分化を促進することによって,基礎細胞癌 (BCC) を治療します. このスムージド阻害剤とWnt経路阻害剤を併用すると,持続的なBCC細胞を根絶し,再発を予防します.
科学分野:
- 腫瘍学
- 皮膚科
- 分子生物学
背景:
- 基礎細胞癌 (BCC) は,異常なヘッジホッグ経路信号によって引き起こされる最も一般的なヒトがんです.
- ビスモデジブのようなスムージド阻害剤はヘッジホグ媒介の癌に使用されますが,BCCの回帰と再発における正確なメカニズムは不明です.
研究 の 目的:
- Smoothenedの阻害がBCC腫瘍の回帰につながるメカニズムを解明する.
- ビジモデジブ治療後の腫瘍再発の細胞基盤を特定し,根絶のための戦略を探求する.
主な方法:
- 基底細胞がんの遺伝子組み換えマウスモデルを 2つ使いました
- 腫瘍細胞の分化に対するヴィスマデギブの影響を調査し,持続的な細胞群を特定した.
- マウスとヒトの両方のBCCサンプルでLGR5発現とWnt信号活性を分析した.
主要な成果:
- ビスマデジブは,毛皮の分化を抑制し,腫瘍細胞の分化を促進することによって,BCCの回帰を媒介する.
- 活動的なWntシグナル伝達を持つ,ゆっくり循環するLGR5発現性腫瘍細胞のサブポピュレーションが持続し,再発を引き起こす.
- ヴィスモデジブとLgr5系統の消去またはWnt抑制による併用治療は,マウスモデルでBCCを根絶した.
結論:
- ビスマデジブは,腫瘍細胞の分化を促進することによって,BCCの回帰を誘導する.
- 持続的なLGR5陽性,Wnt活性腫瘍細胞をターゲットにすることは,再発を防ぐために極めて重要です.
- SmoothenedとWnt経路阻害剤の組み合わせは,BCC再発を克服するための有望な臨床戦略です.
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