CLIN CANCER RES:AZD8186抑制PI3Kβ调节PTEN缺失肿瘤关键代谢通路

2017-12-24 MedSci MedSci原创

PTEN缺失肿瘤依赖PI3Kβ,可以通过选择性PI3Kβ抑制剂AZD8186进行靶向治疗。但是抑制PI3Kβ的结果尚缺乏完整认识。CLIN CANCER RES近期发表了一篇文章研究这一问题。

PTEN缺失肿瘤依赖PI3Kβ,可以通过选择性PI3Kβ抑制剂AZD8186进行靶向治疗。但是抑制PI3Kβ的结果尚缺乏完整认识。CLIN CANCER RES近期发表了一篇文章研究这一问题。

为了研究AZD8186在PTEN缺失肿瘤中的作用,作者对接受AZD8186治疗的PTEN缺失三阴性乳腺癌异种移植模型进行了全基因组RNA-seq分析。在一系列PTEN缺失细胞系和肿瘤模型中研究AZD8186治疗的机制。研究结果表明,AZD8186治疗会导致与细胞代谢相关的转录和蛋白标志改变。研究发现胆固醇合成基因下调和代谢压力相关标志上调。在AZD8186敏感的PTEN缺失细胞系和肿瘤模型中出现胆固醇合成蛋白HMGCS1等的下调。治疗性抑制PI3Kβ还可以上调 PDHK4并增加PDH磷酸化,表明进入TCA循环的碳减少。机制研究发现关键性碳通路、核苷酸和氨基酸合成发生了许多变化。

文章最后认为,该研究发现了PTEN缺失肿瘤PI3Kβ抑制的机制性标志分子,说明靶向PI3Kβ可能影响代谢从而有利于治疗获益。对这些通路的研究有助于发现这类药物的分子标志及联合治疗策略。

原始出处:
James T.Lynch,Urszula M.Polanska,et al.Inhibiting PI3Kβwith AZD8186 Regulates Key Metabolic Pathway in PTEN-Null Tumors.CLIN CANCER RES.December 2017 doi:10.1158/1078-0432.CCR-17-0676

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    2017-12-30 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

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    2017-12-26 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

  4. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-26 xiaogang317
  5. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
  6. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-25 1ddf0692m34(暂无匿称)

    学习了.涨知识

    0

  7. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-25 jefee1214

    已阅.肿瘤代谢或许应该得到更多的关注

    0

  8. 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attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Mon Dec 25 01:24:52 CST 2017, time=2017-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=272131, encodeId=2c9f2e2131f9, content=非常好的文章.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Dec 24 13:18:58 CST 2017, time=2017-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=272120, encodeId=4a4e2e2120a3, content=henhao, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-25 sunfeifeiyang

    学习

    0

  9. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-24 天涯183

    非常好的文章.学习了

    0

  10. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Sun Dec 24 13:16:29 CST 2017, time=2017-12-24, status=1, ipAttribution=)]
    2017-12-24 hhh678

    henhao

    0