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HER2およびHER3変異がん患者におけるHERキナーゼ抑制

David M Hyman¹, Sarina A Piha-Paul², Helen Won¹

¹Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Nature

|February 9, 2018

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PubMed で要約を見る

まとめ

この研究では,ネラチニブを使用した様々ながんにおけるHER2およびHER3変異を調査した. 結果は,がんの種類と変異によって効果が異なることを示し,標的治療の可能性を強調した.

科学分野:

腫瘍学
遺伝学
薬理学について

背景:

ERBB2 (HER2) とERBB3 (HER3) の体内の突然変異は,多くの癌のタイプに共通しています.
いくつかの変異が構成的な HER2 アクティベーションを引き起こすことは知られていますが,ほとんどの生物学的意義は特徴づけられていないままです.
臨床前モデルでは,HER2およびHER3変異の全スペクトルに関する洞察は限られている.

研究の目的:

既知のおよび未知の腫瘍性HER2およびHER3変異の生物学的および治療的重要性を定義する.
パン- HERキナーゼ阻害剤ネラチニブの有効性を遺伝子的に選択された患者群で評価する.
特定の腫瘍型とHER2/HER3変異プロファイルとの臨床結果の相関性.

主な方法:

ネラチニブを用いたマルチヒストロジー"バスケット"臨床試験 (SUMMIT; NCT01953926) を実施した.
ERBB2またはERBB3変異を宿すがんを患った患者
腫瘍組織学と特定の変異の特徴に基づいて治療反応を分析した.

主要な成果:

ネラチニブの有効性は,異なるがんタイプと特定のHER2 / HER3変異によって有意に変化しました.
最も高い治療効果は乳がん,子宮頸がん,胆管がんで観察された.
キナーゼ領域ミッセンスの変異を持つ腫瘍は,顕著な反応を示した.

結論:

分子駆動のバスケット試験は遺伝子変異の生物学的な役割を解明するために不可欠です
ネラティニブは,特定のHER2変異がん,特にミッセンスの変異を持つがんにおいて有望である.
このアプローチは,ゲノム駆動腫瘍学の理解と応用を進めるものです.

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