CDK9をターゲットにすることで,がんにおける表遺伝的に静止された遺伝子が再活性化されます
Hanghang Zhang1, Somnath Pandey1, Meghan Travers2
1Fels Institute for Cancer Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Cell
|November 21, 2018
まとめ
サイクリン依存キナーゼ9 (CDK9) 阻害は,静止された腫瘍抑制遺伝子を再活性化します. このエピジェネティック・セラピーのアプローチは 遺伝子発現を回復し 広範な抗がん活性を示し 癌治療の新たな戦略を提供します
科学分野:
- 分子生物学
- エピジェネティクス
- 癌 研究
背景:
- サイクリン依存キナーゼ9 (CDK9) は,転写延長を促進することが知られている.
- CDK9はヘテロクロマティック領域での遺伝子サイレンシングの維持にも重要な役割を果たします.
研究 の 目的:
- 遺伝子の静止における CDK9の役割を調査する.
- CDK9を標的として,がんに対する新しい治療戦略を発見する.
主な方法:
- 生体細胞の薬物検診と遺伝子検査
- 選択的なCDK9阻害剤 (MC180295) の開発と最適化
- 抗がん活性と免疫チェックポイント阻害剤のインビトロおよびインビボの評価
主要な成果:
- CDK9の阻害は,がん細胞で表遺伝的に静止された遺伝子を再活性化します.
- 腫瘍抑制遺伝子の発現が回復し 細胞の分化が誘発される
- 広範な抗がん効果を持つ高度に選択的なCDK9阻害剤 (MC180295) を開発した.
- CDK9阻害は,α-PD-1免疫療法に対する腫瘍を敏感にします.
結論:
- CDK9は遺伝子静止を維持するために不可欠であり,その抑制はがんに対する有効な表遺伝子療法です.
- 選択的CDK9抑制は,単独および免疫療法と併用して,重要な抗がん能力を示しています.
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