ガンゲノムアトラスの腫瘍性シグナル伝達経路
Francisco Sanchez-Vega1, Marco Mina2, Joshua Armenia1
1Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell
|April 7, 2018
まとめ
がん細胞は 重要な信号伝達経路を 頻繁に変えてしまいます この研究では9,125の腫瘍を分析し,89%が誘導因子の変化,57%が標的となる変化を示し,併用療法の可能性を明らかにした.
科学分野:
- 腫瘍学
- ゲノミクス
- 分子生物学
背景:
- 細胞サイクル,アポトーシス,そして成長経路の遺伝的変化が 癌の特徴です.
- 特定のメカニズムとこれらの変化の同時発生は,腫瘍の種類と個々の腫瘍によって大きく異なります.
研究 の 目的:
- 様々な癌の10の正規の信号伝達経路における体内の変異の状況を包括的に分析する.
- これらの経路の変化の共発生と相互排他性のパターンを特定する.
- 潜在的治療戦略のための標的となる変化を持つ腫瘍の割合を評価する.
主な方法:
- 癌ゲノムアトラス (TCGA) からの9,125の腫瘍のマルチオームデータ (変異,コピー数,mRNA発現,遺伝子融合,DNAメチル化) を利用した.
- 細胞サイクル,Hippo,Myc,Notch,Nrf2,PI-3-キナーゼ/Akt,RTK-RAS,TGFβシグナル伝達,p53,β-カタニン/Wntの10の主要ながん関連経路の変化を分析した.
- 33の癌型と64のサブタイプを分層分析した.
主要な成果:
- 分析された腫瘍の89%は この10の経路内の少なくとも"つの誘導因子の変化を示した.
- 腫瘍の57%は 少なくとも1つの変化を現存の薬で 標的とすることができました
- 腫瘍の30%は複数の標的となる変化を示し 組み合わせ治療の大きな可能性を示唆しています
結論:
- カノニカルシグナル伝達経路は,腫瘍の種類によって特定のパターンが変化する.
- 腫瘍の大部分には 標的となる変化があり 精密医療と組み合わせられた治療戦略の機会を 強調しています
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