併用がん治療は,薬剤添加性やシナジーなしに,患者対患者の可変性によって利益をもたらすことができる
Adam C Palmer1, Peter K Sorger1
1Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 16, 2017
まとめ
患者の多様性によって がん治療薬の組み合わせが成功する理由がわかります 独立した薬物作用により 患者が最も有効な薬に反応すると 併用療法の効果がもたらされますが 必ずしも相乗効果がもたらされるわけではありません
科学分野:
- 腫瘍学
- 薬理学について
- 翻訳医学
背景:
- 組み合わせたがん治療は,治療の有効性を高め,薬剤耐性を克服するように設計されています.
- 臨床試験ではこれらの組み合わせを 遺伝的に多様な患者集団でテストし 変異性を導入しています
- 多くの薬剤の組み合わせの成功に 基づくメカニズムは まだ完全に理解されていません
研究 の 目的:
- 併用がん治療の成功における患者対患者の変動と独立した薬物作用の役割を調査する.
- 薬剤の組み合わせの臨床的効果を観察するために,相乗効果や添加性が必要かどうかを判断する.
- 臨床試験データを解釈し,将来の組み合わせ治療法を設計するための新しい枠組みを提案する.
主な方法:
- FDAが承認した薬の組み合わせに関する臨床試験データの数学モデルと分析.
- 患者からの腫瘍異種移植モデルにおける組み合わせ治療の評価
- 多様な患者集団における薬剤の相乗効果,添加性,および独立した作用の評価.
主要な成果:
- 患者から患者への変化と薬物による独立した作用は,多くの承認された薬剤の組み合わせの有効性を十分に説明します.
- 臨床前モデルでシナジーや添加性が示唆された場合でも,薬物による独立した作用が臨床集団で支配的なメカニズムであることが観察されました.
- この現象は患者による腫瘍異種移植の研究でも明らかでした.
結論:
- 多くの併用がん治療の成功は,相乗効果の相互作用ではなく,個々の薬に対する患者特有の反応に起因する.
- 患者の変異性の文脈における 薬物による独立した作用を理解することは 臨床試験の結果を解釈する新たな視点を提供する.
- この洞察は,個々の患者の腫瘍の感受性に基づいて治療選択を最適化するために,組み合わせ治療の設計を再評価することを必要とします.
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