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CLIN CANCER RES：靶向去势抵抗前列腺癌中的BET家族蛋白

2018-07-07 MedSci MedSci原创

去势抵抗前列腺癌BET蛋白治疗靶点
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持续的雄激素受体信号会促进去势抵抗前列腺癌进展以及雄激素受体（AR）靶向治疗耐药。需要克服这一障碍的治疗策略。CLIN CANCER RES近期发表了一篇文章，评估BET蛋白抑制剂（BETi）是否可以消除去势抵抗前列腺癌中异常的雄激素受体信号。

持续的雄激素受体信号会促进去势抵抗前列腺癌进展以及雄激素受体（AR）靶向治疗耐药。需要克服这一障碍的治疗策略。CLIN CANCER RES近期发表了一篇文章，评估BET蛋白抑制剂（BETi）是否可以消除去势抵抗前列腺癌中异常的雄激素受体信号。

作者分析了BET表达，雄激素受体诱导的转录情况以及患者结局情况，在前列腺癌模型中研究化学性BETi（JQ1和GSK1210151A；I-BET151）以及BET家族蛋白敲低对AR-V7表达和AR信号的调节情况。研究结果表明，同一患者的治疗前标本和去势抵抗前列腺癌标本中，随着趋势抵抗出现核BRD4蛋白表达显着增加，且诊断时表达水平高于预后较差有关。去势抵抗前列腺癌标本中BRD2，BRD3和BRD4 RNA表达与AR诱导的转录有关。此外，BETi调节RNA进程从而减低AR-V7表达。BETi还可以抑制前列腺癌细胞生长，AR扩增和AR-V7表达。最后，研究还发现BETi可以降低持续的AR信号，并在存在AR扩增和AR-V7表达的去势抵抗前列腺癌异种移植模型中抑制肿瘤生长。

文章最后认为，BETi作为AR信号和功能抑制剂需要进一步的临床评估，以研究阻断的药理学机制。

原始出处：
Jonathan Welti,Adam Sharp,et al.Targeting Bromodomain and Extra-Terminal(BET) Family Proteins in Castration-Resistant Prostate Cancer(CRPC).CLIN CANCER RES.July 2018 doi:10.1158/1078-0432.CCR-17-3571

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    2019-06-01 more is better!

    #去势抵抗前列腺癌#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1946673, encodeId=8c8e19466e36b, content=<a href='/topic/show?id=e61f3e232f7' target=_blank style='color:#2F92EE;'>#去势抵抗前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37232, encryptionId=e61f3e232f7, topicName=去势抵抗前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca6a2500099, createdName=more is better!, createdTime=Sat Jun 01 21:01:00 CST 2019, time=2019-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760746, encodeId=b29c1e60746d1, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Dec 11 09:01:00 CST 2018, time=2018-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330307, encodeId=a27f33030e0c, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2018/07/09/9d6ae4a345db0c5799f866ac5743fbc0.jpg, createdBy=0ba62073690, createdName=GZphD9, createdTime=Mon Jul 09 06:31:37 CST 2018, time=2018-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330124, encodeId=530f33012475, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Jul 08 09:02:11 CST 2018, time=2018-07-08, status=1, ipAttribution=)]
    2018-12-11 ms5439512287675881

    #BET#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1946673, encodeId=8c8e19466e36b, content=<a href='/topic/show?id=e61f3e232f7' target=_blank style='color:#2F92EE;'>#去势抵抗前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37232, encryptionId=e61f3e232f7, topicName=去势抵抗前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca6a2500099, createdName=more is better!, createdTime=Sat Jun 01 21:01:00 CST 2019, time=2019-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760746, encodeId=b29c1e60746d1, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Dec 11 09:01:00 CST 2018, time=2018-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330307, encodeId=a27f33030e0c, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2018/07/09/9d6ae4a345db0c5799f866ac5743fbc0.jpg, createdBy=0ba62073690, createdName=GZphD9, createdTime=Mon Jul 09 06:31:37 CST 2018, time=2018-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330124, encodeId=530f33012475, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Jul 08 09:02:11 CST 2018, time=2018-07-08, status=1, ipAttribution=)]
    2018-07-09 GZphD9

    学习了.谢谢分享

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1946673, encodeId=8c8e19466e36b, content=<a href='/topic/show?id=e61f3e232f7' target=_blank style='color:#2F92EE;'>#去势抵抗前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37232, encryptionId=e61f3e232f7, topicName=去势抵抗前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca6a2500099, createdName=more is better!, createdTime=Sat Jun 01 21:01:00 CST 2019, time=2019-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760746, encodeId=b29c1e60746d1, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Dec 11 09:01:00 CST 2018, time=2018-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330307, encodeId=a27f33030e0c, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2018/07/09/9d6ae4a345db0c5799f866ac5743fbc0.jpg, createdBy=0ba62073690, createdName=GZphD9, createdTime=Mon Jul 09 06:31:37 CST 2018, time=2018-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330124, encodeId=530f33012475, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Jul 08 09:02:11 CST 2018, time=2018-07-08, status=1, ipAttribution=)]
    2018-07-08 kafei

    学习了谢谢

    0

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