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Eur Urol：向精密泌尿系肿瘤学方向迈进，一种新型的AR拮抗剂

2017-08-28 fengxiangxin MedSci原创

前列腺癌去势抵抗性前列腺癌恩杂鲁胺耐药AR突变ODM-201
关注

Darolutamide（ODM-201）是一种新型的雄激素受体（AR）拮抗剂，其化学结构与目前批准的AR拮抗剂有明显差异，主要针对野生型和突变型的配体结合域突变体抑制AR核转位。

Darolutamide（ODM-201）是一种新型的雄激素受体（AR）拮抗剂，其化学结构与目前批准的AR拮抗剂有明显差异，主要针对野生型和突变型的配体结合域突变体抑制AR核转位。

在本研究中，研究者评估了在恩杂鲁胺耐药的去势抵抗性前列腺癌（CRPC）和恩杂鲁胺、阿比特龙或比卡鲁胺治疗后检测到有AR突变的患者中ODM-201的活性。体外实验中，ODM-201显著抑制了恩杂鲁胺抵抗的MR49F细胞的生长以及AR的转录活性。体内实验中，ODM-201导致了肿瘤体积的减小和血清SPA水平的降低，延长了异种移植恩杂鲁胺抵抗的MR49F细胞后小鼠的生存期。

此外，ODM-201抑制了在传统治疗后进展的CRPC患者的血清AR突变体的转录活性。特别地，ODM-201显著抑制了F877L、H875Y/T878A、F877L/T878A和先前未报道的T878G AR 突变的转录活性。硅片化学信息计算机模拟提供了原子水平的证据证明ODM-201对 F877L和T878G AR突变的拮抗作用。

总之，该项研究结果为评估ODM-201用于恩杂鲁胺耐药的CRPC患者，特别是联合精密肿瘤学和循环肿瘤DNA检测对ODM-201敏感的AR突变提供了进一步的临床理论基础。

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    2017-09-03 1dd8f26bm82(暂无匿称)

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    0

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    2017-09-02 1dd8f26bm82(暂无匿称)

    好资源

    0

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    2017-09-01 1dd8f26bm82(暂无匿称)

    好资源

    0

  4. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-31 1dd8f26bm82(暂无匿称)

    好资源

    0

  5. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-10-09 hxj0130

    #泌尿系肿瘤#

    0

  6. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-30 108807375_62823127

    #肿瘤学#

    0

  7. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-30 yhy100202

    #泌尿系#

    0

  8. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-30 ms5236388012055669

    #拮抗剂#

    0

  9. 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createdBy=18b32500069, createdName=108807375_62823127, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459851, encodeId=932e145985132, content=<a href='/topic/show?id=83ec64e7814' target=_blank style='color:#2F92EE;'>#泌尿系#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64778, encryptionId=83ec64e7814, topicName=泌尿系)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=182b6204426, createdName=yhy100202, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511680, encodeId=d5a3151168017, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Wed Aug 30 09:01:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238474, encodeId=76642384e42b, content=学习过了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好！, createdTime=Wed Aug 30 00:40:49 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=238154, encodeId=176123815440, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-30 明天会更好！

    学习过了.谢谢分享!

    0

  10. 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attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4FADCE0F987688.jpg, createdBy=23af1632396, createdName=1dd8f26bm82(暂无匿称), createdTime=Tue Aug 29 00:47:28 CST 2017, time=2017-08-29, status=1, ipAttribution=)]
    2017-08-29 1dd8f26bm82(暂无匿称)

    好资源

    0

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