Neurological Surgery 脳神経外科36巻1号

2008年01月発行

連載 悪性脳腫瘍治療の今とこれから

1．悪性神経膠腫の遺伝子解析とその臨床応用

著者： 溝口昌弘¹ 庄野禎久¹

所属機関： ¹九州大学大学院医学研究院脳神経外科

ページ範囲：P.83 - P.91

Ⅰ．はじめに

　悪性神経膠腫は原発性脳腫瘍において最も頻度の高い腫瘍の1つであり，近年の診断・治療技術の進歩にも関わらず，未だ十分な治療成績が得られていないのが現状である．特に最も悪性度の高いglioblastoma（GBM）に関しては，現在でも平均生存期間が1年前後とヒト悪性腫瘍のなかで最も難治性の腫瘍の1つである^61,66)．他臓器に発生する腫瘍と比べてもその増殖能，浸潤能は高く，発生母地である脳の機能温存，血液脳関門という大きな障壁があり，他臓器腫瘍とは一線を画した独自の治療戦略確立が必要である⁶⁴⁾．腫瘍が遺伝子の異常により発生することが認識され，悪性神経膠腫に関してもこれまで多くの遺伝子異常が報告されてきた^44,45,54)．悪性神経膠腫の治療戦略を立てるうえで，安全かつ可及的広範な腫瘍摘出に加え，正確な病理診断，遺伝子解析に基づく適正な補助療法を行うことが重要である．特に遺伝子異常に基づく個別化治療の開発には，正確で迅速な病理診断，遺伝子診断を随時臨床にフィードバックできるシステム構築が必要である．近年，第2世代のアルキル化剤であるtemozolomideやさまざまなシグナル伝達系を標的とした分子標的治療による悪性神経膠腫に対する治療効果が報告されているが，決して満足できるものではない^66,68)．現在，遺伝子プロファイルに基づき，これらの治療の有効性に差が認められることが報告され，遺伝子解析の重要性が明らかとなっている^24,28,49)．さらに治療抵抗性の機序を裏付ける概念として種々の腫瘍でcancer stem cell（CSC）の存在が証明され⁵⁶⁾，新たな遺伝子制御機序であるmicroRNA（miRNA）が発見されたことに伴い腫瘍の遺伝子解析，分子生物学的研究も新たな局面を迎えている．本稿では，悪性神経膠腫治療に対する遺伝子解析，遺伝子異常に基づく治療の現状と今後の展望について概説する．

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