去勢抵抗性前立腺癌（CRPC）に対する新規治療法の確立には，再燃メカニズムの解明は必要不可欠である．共にユビキチン-プロテアソーム系によって制御される転写因子NF-kappa Bのシグナル伝達系と小胞体ストレス応答系という新たな観点から前立腺癌の再燃メカニズムの解明を試みた．再燃メカニズムの１つとして，NF-kappa Bの恒常的な活性化と小胞体ストレスからの継続的な回避が示されたと共に，ユビキチン-プロテアソーム系を創薬標的とした治療戦略がCRPCに対する新規治療となりうる可能性も示唆された．
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 investigated the mechanism for the emersion of CRPC from the perspective of ubiquitin-proteasome system regulating both NF-kappa B and unfolded protein response (UPR) activation. Our study suggested that constitutive NF-kappa B activation and successive escape from endoplasmic reticulum stress might be one of mechanism for CRPC emersion, and that trying development of new drugs with targeting for ubiquitin-proteasome system might be a novel therapeutic strategy for the management of CRPC.
去勢抵抗性前立腺癌に対するユビキチン－プロテアソーム系を標的とした治療戦略の確立
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HO-PR-KONAKA-H-kaken 2017-5p.pdf
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