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口腔がんの治療抵抗性の解明と新規治療法の開発に関する研究

　「口腔がん」の研究は当教室における研究の柱です。口腔がんに対する治療として、手術療法、放射線療法、化学療法、免疫療法を組み合わせる集学的治療が行われます。悪性度の高い口腔がんは転移や再発を生じやすく、さまざまな治療に抵抗性を示して患者さんの命を奪うため、治療の上で大きな問題となっています。そこで私たちは、口腔がん治療における以下の４つの課題を最重要テーマとし、研究に取り組んでいます。

  1. 浸潤・転移
  2. 放射線抵抗性
  3. 抗がん剤耐性
  4. 免疫療法抵抗性

　放射線療法は、手術療法の次にがんの局所制御に優れた治療法ですが、「放射線抵抗性」を示す口腔がんの研究は、これまでほとんど行われていません。しかしながら、再発リスクの高い口腔がん患者に対して放射線療法を行うことが多く、その治療効果が患者さんの生命予後を大きく左右することから、口腔がんの「放射線抵抗性」メカニズムを解明することは非常に重要です。以上のような理由から、当教室では現在「放射線抵抗性」についての研究を重視しています。口腔がんの「放射線抵抗性」についての当教室からの初めての研究成果は英文誌に掲載され（Matsuoka et al, Br J Cancer, 2016）、本研究の記事は、サイエンス誌の出版元AAASによる世界最大規模の科学プレスリリースwebサイト「EurekAlert!」で紹介されました（プレスリリースはこちら）。

　また当教室では、これまで口腔・咽頭がんに対する免疫療法としてペプチドワクチン療法を全国に先駆けて実施し、口腔がんに対する免疫療法の有用性を示しました（Yoshitake et al, Clin Cancer Res, 2015）。2018年に免疫療法の研究がノーベル医学・生理学賞に輝き、免疫療法への注目度は以前よりも更に高まっています。ノーベル賞に関連のある免疫チェックポイント阻害薬（オプジーボ）を口腔がん患者に投与すると、過去に経験のないがんの治療効果を目の当たりにするようになりました。投与患者の全例で良好な結果が得られるわけではありませんが、今後は免疫療法の治療効果の予測を可能にすることが重要です。そこで私たちは、免疫療法に抵抗性を示す口腔がんについて、「免疫細胞による攻撃からの回避機構」を明らかにし、免疫療法の効果の予測や効果の増強を可能にすることが目標です。

　一般にがんの特徴は、多段階で進行する際に初期がん細胞が獲得する8つの生物学的能力によって合理的に説明できます。その8つの能力とは、持続的な増殖シグナル、増殖抑制因子の回避、細胞死への抵抗性、無限の細胞複製能、血管新生の誘導、浸潤と転移の活性化、エネルギー代謝のリプログラミング、免疫による破壊の回避、です。当教室では、既に述べた口腔がん治療における4つの課題（浸潤・転移、放射線抵抗性、抗がん剤耐性、免疫療法抵抗性）の克服に向けて、これらの8つのがんの特徴を念頭に置きながら、さまざまな実験を行っています。

　今後も口腔がんの患者さんの貴重な臨床検体や臨床データを用いて多角的な視点で基礎的研究を進め、新たな治療法の開発につなげたいと考えています。

参考論文

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