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Nat Med：肿瘤特异性SPOP突变与BET治疗敏感性差异

2017-08-21 zhangfan MedSci原创

子宫内膜癌前列腺癌SPOP
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研究揭示了肿瘤源性突变差异，即不同肿瘤的相同结构域突变导致不同的药物敏感性

一般认为，癌症驱动基因复发性突变会影响药物疗效。癌症基因组研究发现，在子宫内膜和前列腺癌的底物识别域均存在复发性非错义突变，会对泛素连接酶适配器SPOP产生影响，但二者对Bet抑制剂的应答却完全不同。近日研究人员发现，子宫内膜癌相关SPOP 突变会引发泛素蛋白的分子景观发生改变，BRD2， BRD3以及BRD4蛋白(BETs) 作为SPOP–CUL3底物会被子宫内膜癌相关SPOP 突变优先降解，导致BET蛋白水平降低，增加癌细胞对BET抑制剂的敏感性。与之相反，前列腺癌相关SPOP 突变导致受损的BET降解，产生药物抵抗。研究揭示了肿瘤源性突变差异，即不同肿瘤的相同结构域突变导致不同的药物敏感性，该研究解释了长期以来困扰医药学术界的问题：同样的SPOP 突变，为何BET 抑制剂对子宫内膜癌有效，但却对前列腺癌无效？原始出处：Hana Janouskova et al. Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhib

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    2017-09-15 ms5439512287675881

    #BET#

    0

  2. 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    2017-09-22 yeye5224612

    #ET治疗#

    0

  3. 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    2018-03-19 liye789132251

    #Nat#

    0

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href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1607954, encodeId=200f160e95464, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235880, encodeId=b672235880ee, content=学习了很有用不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Tue Aug 22 06:30:18 CST 2017, time=2017-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235787, encodeId=48be235e87f8, content=学习受益匪浅.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Aug 21 20:44:20 CST 2017, time=2017-08-21, status=1, ipAttribution=)]
    2018-04-21 jinweidong

    #特异性#

    0

  5. 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href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1607954, encodeId=200f160e95464, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Aug 21 20:44:20 CST 2017, time=2017-08-21, status=1, ipAttribution=)]
    2018-04-09 ms8888626721583891

    #SPOP#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1760173, encodeId=6f501e601733d, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Fri Sep 15 09:07:00 CST 2017, time=2017-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785867, encodeId=a2911e8586755, content=<a href='/topic/show?id=4cd7e0744b' target=_blank style='color:#2F92EE;'>#ET治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7074, encryptionId=4cd7e0744b, topicName=ET治疗)], attachment=null, authenticateStatus=null, createdAvatar=, 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href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1607954, encodeId=200f160e95464, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235880, encodeId=b672235880ee, content=学习了很有用不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Tue Aug 22 06:30:18 CST 2017, time=2017-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235787, encodeId=48be235e87f8, content=学习受益匪浅.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Aug 21 20:44:20 CST 2017, time=2017-08-21, status=1, ipAttribution=)]
    2017-08-23 ms5236388012055669

    #敏感性#

    0

  7. 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authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Aug 23 11:07:00 CST 2017, time=2017-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235880, encodeId=b672235880ee, content=学习了很有用不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Tue Aug 22 06:30:18 CST 2017, time=2017-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235787, encodeId=48be235e87f8, content=学习受益匪浅.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Aug 21 20:44:20 CST 2017, time=2017-08-21, status=1, ipAttribution=)]
    2017-08-23 仁医06

    #Med#

    0

  8. 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createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Aug 21 20:44:20 CST 2017, time=2017-08-21, status=1, ipAttribution=)]
    2017-08-22 飛歌

    学习了很有用不错

    0

  9. 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    2017-08-21 清风拂面

    学习受益匪浅.谢谢分享

    0

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