Project DRIVE: 大規模で深遠なRNAiスクリーニングによって発見されたがん依存症と合成的致死性関係のまとめ
E Robert McDonald1, Antoine de Weck1, Michael R Schlabach1
1Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.
Cell
|July 29, 2017
まとめ
この研究では 398の癌細胞系から 7,837の遺伝子を検出して がん依存性をマッピングしています この発見は,特に腫瘍抑制遺伝子の喪失に対して,がん治療の新たな治療標的を特定しています.
科学分野:
- 癌 生物学
- ゲノミクス
- 薬物の発見
背景:
- がん変異の理解の進歩は 標的型療法につながりました
- しかし,腫瘍抑制遺伝子の喪失に関連する脆弱性を特定することは依然として困難です.
研究 の 目的:
- 大規模なRNA干渉 (RNAi) スクリーンを実施し,がん依存性を特定する.
- 様々な癌のサブタイプ,特に腫瘍抑制遺伝子の喪失を含む新しい治療標的を発見する.
主な方法:
- 大規模なRNAiスクリーンは398の癌細胞系で行われました.
- 平均して1遺伝子あたり20個の短いヘアピンRNA (shRNA) を使って7,837個の遺伝子を倒した生存効果が評価されました.
主要な成果:
- 癌依存性遺伝子の分類と遺伝子,発現,系統の特徴との相関性
- タンパク質複合体と経路の協力を含む遺伝子の相互作用ネットワークの特徴
- コミュニティの利用のために包括的なデータセットとウェブポータルが作成されました.
結論:
- この研究は新しいがん治療薬の発見と翻訳に 価値あるリソースを提供します
- 特定された依存性は,腫瘍抑制遺伝子の喪失に対抗し,がん治療戦略を改善するための潜在的な標的を提供します.
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