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CLIN CANCER RES：肢端黑色素瘤CDK4通路基因改变表明CDK4/6抑制可以作为靶向疗法

2017-11-23 MedSci MedSci原创

肢端黑色素瘤CDK4基因改变靶向治疗
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不同人群间黑色素瘤亚型分布差异很大。在亚洲人群中，肢端黑色素瘤约占所有黑色素瘤的47.5%-65%。但是对转移性肢端黑色素瘤尚缺乏有效的系统治疗手段。CLIN CANCER RES近期发表了一篇文章，研究肢端黑色素瘤CDK4通路基因改变并评估CDK4/6抑制靶向治疗肢端黑色素瘤的疗效。

不同人群间黑色素瘤亚型分布差异很大。在亚洲人群中，肢端黑色素瘤约占所有黑色素瘤的47.5%-65%。但是对转移性肢端黑色素瘤尚缺乏有效的系统治疗手段。CLIN CANCER RES近期发表了一篇文章，研究肢端黑色素瘤CDK4通路基因改变并评估CDK4/6抑制靶向治疗肢端黑色素瘤的疗效。

作者共检测了514例肢端黑色素瘤样本的CDK4通路相关基因拷贝数变化（CNV），包括Cdk4，Ccnd1，和P16INK4a。评估肢端黑色素瘤细胞系及异种移植模型对CDK4/6抑制剂的敏感性。研究结果表明，在514例样本中，203例有Cdk4获得，137例有Ccnd1获得，310例有P16INK4a缺失。至少含有Cdk4，Ccnd1，P16INK4a其中一种基因改变的肢端黑色素瘤占82.7%。同时存在Cdk4获得和P16INK4a缺失的肢端黑色素瘤患者与无此变化的患者相比平均总生存时间显着降低。pan-CDK抑制剂AT7519和选择性CDK4/6抑制剂PD0332991可以抑制肢端黑色素瘤细胞系活性，抑制Cdk4获得+Ccnd1获得、Cdk4获得+P16INK4a缺失和Ccnd1获得+P16INK4a缺失异种移植模型的肿瘤生长。

文章最后认为，肢端黑色素瘤中常见CDK通路基因改变。肢端黑色素瘤细胞系和含有CDK通路改变的异种移植模型对CDK4/6抑制剂敏感。该研究结果为CDK4/6抑制剂治疗肢端黑色素瘤患者提供了证据。

原始出处：
Yan Kong,Xinan Sheng,et al.Frequent Genetic Aberrtions in the CDK4 Pathway in Acral Melanoma Indicate the Potential for CDK4/6 Inhibitors in Targeted Therapy.CLIN CANCER RES.November 2017 doi:10.1158/1078-.432.CCR-17-0070

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    2018-03-08 珙桐

    #肢端黑色素瘤#

    0

  2. 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    2018-07-28 12498adam51暂无昵称

    #基因改变#

    0

  3. 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2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558855, encodeId=b78315588554f, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564864, encodeId=c97d1564864bc, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2018-07-28 soongzhihua

    #CDK4#

    0

  4. 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2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558855, encodeId=b78315588554f, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564864, encodeId=c97d1564864bc, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2018-06-12 sunylz

    #色素#

    0

  5. 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2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558855, encodeId=b78315588554f, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564864, encodeId=c97d1564864bc, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2017-11-25 yanghan

    #靶向疗法#

    0

  6. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4399, encryptionId=09dc439915, topicName=CDK)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1490683, encodeId=4ccd149068305, content=<a href='/topic/show?id=2765440372' target=_blank style='color:#2F92EE;'>#CDK4/6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4403, encryptionId=2765440372, topicName=CDK4/6)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c7068807080, createdName=zhangj7111, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558855, encodeId=b78315588554f, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564864, encodeId=c97d1564864bc, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2017-11-25 zhouqu_8

    #CDK#

    0

  7. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4399, encryptionId=09dc439915, topicName=CDK)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1490683, encodeId=4ccd149068305, content=<a href='/topic/show?id=2765440372' target=_blank style='color:#2F92EE;'>#CDK4/6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4403, encryptionId=2765440372, topicName=CDK4/6)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c7068807080, createdName=zhangj7111, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558855, encodeId=b78315588554f, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564864, encodeId=c97d1564864bc, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2017-11-25 zhangj7111

    #CDK4/6#

    0

  8. 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    2017-11-25 cqlidoudou

    #黑色素#

    0

  9. 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authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sat Nov 25 00:54:00 CST 2017, time=2017-11-25, status=1, ipAttribution=)]
    2017-11-25 cqlidoudou

    #黑色素#

    0