CLIN CANCER RES:HER2+乳腺癌HER2靶向治疗耐药机制

2017-09-12 MedSci MedSci原创

HER2+乳腺癌抗HER2治疗可能通过其他通路活化或HER信号通路再激活导致耐药。CLIN CANCER RES近期发表了一篇文章,使用BT474亲代和治疗抵抗细胞系模型研究在HER2靶向治疗时HER2+乳腺癌再激活HER网络的机制。

HER2+乳腺癌抗HER2治疗可能通过其他通路活化或HER信号通路再激活导致耐药。CLIN CANCER RES近期发表了一篇文章,使用BT474亲代和治疗抵抗细胞系模型研究在HER2靶向治疗时HER2+乳腺癌再激活HER网络的机制。

作者使用ER+/HER2+BT474细胞系(AZ/ATCC)诱导lapatinib(L)耐药、trastuzumab(T)耐药及联合耐药(LR/TR/LTR)。与亲代细胞系相比,利用平行测序研究耐药细胞系(BT474/AZ-LR和BT474/ATCC-LTR)出现耐药时是否存在HER2再激活。利用异位表达和突变特异性siRNA干扰分析突变功能。在体内和体外实验中检测突变HER2抑制的治疗方案。研究结果表明,耐药细胞系BT474/AZ-LR和BT474/ATCC-LTR中唯一常见的体细胞突变为HER2L755S。HER2L755S异位表达在BT474/AZ,SK-BR-3和AU565亲代细胞系中可以诱导lapatinib耐药。HER2L755S特异性siRNA敲除可以逆转BT474/AZ-LR和BT474/ATCC-LTR细胞系耐药情况。在体内和体外实验中,HER1/2不可逆抑制剂afatinib和neratinib可以持续抑制耐药细胞生长和HER2L755S诱导的HER2及下游AKT/MAPK信号。

文章最后认为,HER2L755S突变导致的HER2再激活是lapatinib HER2靶向治疗耐药的机制之一,这种耐药作用可以被不可逆HER1/2抑制剂克服。

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1971349, encodeId=83f419e134988, content=<a href='/topic/show?id=ee288039ece' target=_blank style='color:#2F92EE;'>#耐药机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80397, encryptionId=ee288039ece, topicName=耐药机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Jul 06 10:20:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243247, encodeId=9ef424324ef4, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Tue Sep 12 16:30:32 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243209, encodeId=a15d24320933, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Tue Sep 12 12:39:44 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243176, encodeId=d85a2431e6ad, content=谢谢分享. , beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 12 10:12:47 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243152, encodeId=5099243152f8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=98dd1959726, createdName=游手好闲, createdTime=Tue Sep 12 08:55:26 CST 2017, time=2017-09-12, status=1, ipAttribution=)]
    2017-09-12 luominglian113

    学习了.谢谢分享

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1971349, encodeId=83f419e134988, content=<a href='/topic/show?id=ee288039ece' target=_blank style='color:#2F92EE;'>#耐药机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80397, encryptionId=ee288039ece, topicName=耐药机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Jul 06 10:20:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243247, encodeId=9ef424324ef4, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Tue Sep 12 16:30:32 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243209, encodeId=a15d24320933, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Tue Sep 12 12:39:44 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243176, encodeId=d85a2431e6ad, content=谢谢分享. , beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 12 10:12:47 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243152, encodeId=5099243152f8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=98dd1959726, createdName=游手好闲, createdTime=Tue Sep 12 08:55:26 CST 2017, time=2017-09-12, status=1, ipAttribution=)]
    2017-09-12 清风拂面

    谢谢分享.学习了

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1971349, encodeId=83f419e134988, content=<a href='/topic/show?id=ee288039ece' target=_blank style='color:#2F92EE;'>#耐药机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80397, encryptionId=ee288039ece, topicName=耐药机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Jul 06 10:20:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243247, encodeId=9ef424324ef4, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Tue Sep 12 16:30:32 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243209, encodeId=a15d24320933, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Tue Sep 12 12:39:44 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243176, encodeId=d85a2431e6ad, content=谢谢分享. , beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 12 10:12:47 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243152, encodeId=5099243152f8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=98dd1959726, createdName=游手好闲, createdTime=Tue Sep 12 08:55:26 CST 2017, time=2017-09-12, status=1, ipAttribution=)]
    2017-09-12 doctorJiangchao

    谢谢分享.

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1971349, encodeId=83f419e134988, content=<a href='/topic/show?id=ee288039ece' target=_blank style='color:#2F92EE;'>#耐药机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80397, encryptionId=ee288039ece, topicName=耐药机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Jul 06 10:20:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243247, encodeId=9ef424324ef4, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Tue Sep 12 16:30:32 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243209, encodeId=a15d24320933, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Tue Sep 12 12:39:44 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243176, encodeId=d85a2431e6ad, content=谢谢分享. , beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 12 10:12:47 CST 2017, time=2017-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243152, encodeId=5099243152f8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=98dd1959726, createdName=游手好闲, createdTime=Tue Sep 12 08:55:26 CST 2017, time=2017-09-12, status=1, ipAttribution=)]
    2017-09-12 游手好闲

    学习了

    0

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