A novel treatment strategy for castration-refractory prostate cancer targeting cross-talk between NFκB and an intranuclear steroid receptor superfamily
去勢抵抗性前立腺癌に対する新規治療法の確立には，再燃メカニズムの包括的解明は必要不可欠である．核内ステロイド受容体スーパーファミリーに属する，アンドロゲン受容体，グルココルチコイド受容体，エストロゲン受容体の転写系と転写因子NF-κBのシグナル伝達系のクロストークという新たな観点から前立腺癌再燃メカニズムを解明した．また，そのクロストークを標的とした各種シグナル伝達阻害技術を駆使して，去勢抵抗性前立腺癌に対する集学的治療戦略を構築した．さらに，各核内受容体間における転写系シグナル伝達ネットワークの存在が明らかにされ，同クロストークはCRPCに対する新規標的治療となりうる可能性が示唆された．
Elucidating a comprehensive mechanism through which most patients with advanced prostate cancer have an initial response to androgen deprivation therapy, but eventually progress to a castration-resistant state is critical to establish a novel treatment strategy for castration refractory prostate cancer (CRPC). We investigate the mechanism of CRPC from the perspective of some cross-talks in signal transduction pathway between NF-kB and an intranuclear steroid receptor superfamily containing androgen receptor, glucocorticoid receptor, and estrogen receptor. Also we target the cross-talk with various methods of inhibiting the signaling transduction pathway and established the integrated treatment strategy of CRPC. Consequently, our study made it clear that cross-talk between NF-kB and an intranuclear steroid receptor superfamily might existence, and also suggested inhibiting the cross-talk of signaling pathway network might be novel therapeutics for the management of CRPC.
核内受容体・NF－κBクロストークを標的とした去勢抵抗性前立腺癌に対する治療戦略
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HO-PR-KONAKA-H-kaken 2014-5p.pdf
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