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Br J Cancer：sapanisertib治疗晚期实体瘤

2020-09-15 QQY MedSci原创

晚期实体瘤sapanisertib
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PI3K/AKT/mTOR信号转导通路参与调节细胞生长、增殖和存活。 在人癌症中经常能观察到异常的PI3K/AKT/mTOR信号。抑制mTOR会减少蛋白质的翻译并预防异常细胞的增殖和肿瘤血管生成作用。

PI3K/AKT/mTOR信号转导通路参与调节细胞生长、增殖和存活。 在人癌症中经常能观察到异常的PI3K/AKT/mTOR信号。抑制mTOR会减少蛋白质的翻译并预防异常细胞的增殖和肿瘤血管生成作用。

Sapanisertib是一种高选择性的mTOR激酶抑制剂，其可以同时抑制mTORC1和mTORC2。 该1期剂量递增/扩展研究主要评估晚期实体瘤患者口服sapanisertib的安全性和耐受性。


受试患者分为四组进行sapanisertib剂量递增给药，给药方案如下，每日一次（QD，31位患者）；每周一次（QW，30位患者）；吃三天停4天（QD×3dQW，33位患者）；吃5天停2天（QD×5dQW，22例患者）。在扩展队列中，患肾细胞癌（RCC）、子宫内膜癌或膀胱癌的共82位患者接受5mg QD（39位）、40μmg QW（26位）或30μmg QW（17位）的sapanisertib给药治疗。

Sapanisertib的药代动力学结果图

结果显示，Sapanisertib的最大耐受剂量为6μmg QD、40μmg QW、9μmg QD×3dQW和7μmg QD×5dQW。常见的剂量限制性毒性（DLTs）包括高血糖症、黄斑丘疹（QD）、乏力和口腔炎（QD×3dQW/QD×5dQW）；根据DLT评估的耐受性分析，选择5μmg QD和30μmg QW进行扩展队列的给药研究。一位RCC患者获得完全缓解；9位患者获得部分缓解（其中肾细胞癌患者7位；膀胱癌和子宫内膜癌各1位）。药代动力学显示，Sapanisertib是时间线性的，并支持重复给药。药效学研究结果表明，与治疗相关的TORC1/2生物标志物减少。


综上，在该1期研究中，药物Sapanisertib显示出可控的安全性，且在肾细胞癌和子宫内膜癌中观察到初步的抗肿瘤活性。


原始出处：

Voss, M.H., Gordon, M.S., Mita, M. et al. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer (11 September 2020).

 

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    2021-04-30 MedSciZeng

    #Br J Cancer#点击查看更多相关话题 或评论点击插入您喜欢的话题

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=961878, encodeId=42639618e820, content=<a href='/topic/show?id=d12d1042620a' target=_blank style='color:#2F92EE;'>#Br J Cancer#</a>点击查看更多相关话题 或评论点击插入您喜欢的话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=104262, encryptionId=d12d1042620a, topicName=Br J Cancer)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20221103/2796e00c9b4549e3b313ed9e7accc68f/b52d6d98bbe04782b5a4e2dd1ee80be2.jpeg, createdBy=078e1614372, createdName=MedSciZeng, createdTime=Fri Apr 30 17:23:34 CST 2021, time=2021-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1898190, encodeId=31db189819044, content=<a href='/topic/show?id=8904158e9e7' target=_blank style='color:#2F92EE;'>#SAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15879, encryptionId=8904158e9e7, topicName=SAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30f5146, createdName=zz70, createdTime=Thu Feb 04 12:27:48 CST 2021, time=2021-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886230, encodeId=79658862304d, content=Sapanisertib显示出可控的安全性，且在肾细胞癌和子宫内膜癌中观察到初步的抗肿瘤活性。, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=qinqiyun, createdTime=Thu Sep 17 23:52:10 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338223, encodeId=c812133822335, content=<a href='/topic/show?id=cd2a262068' target=_blank style='color:#2F92EE;'>#APA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2620, encryptionId=cd2a262068, topicName=APA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ce072500140, createdName=12498b3em08(暂无昵称), createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1443150, encodeId=747214431505e, content=<a href='/topic/show?id=feee598219f' target=_blank style='color:#2F92EE;'>#晚期实体瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59821, encryptionId=feee598219f, topicName=晚期实体瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55065029738, createdName=446798725_87912766, createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885664, encodeId=73558856645c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Wed Sep 16 08:19:15 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885573, encodeId=123a8855e3ec, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Tue Sep 15 21:58:58 CST 2020, time=2020-09-15, status=1, ipAttribution=)]
    2021-02-04 zz70

    #SAP#

    0

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    2020-09-17 qinqiyun

    Sapanisertib显示出可控的安全性，且在肾细胞癌和子宫内膜癌中观察到初步的抗肿瘤活性。

    0

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    2020-09-17 12498b3em08(暂无昵称)

    #APA#

    0

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    2020-09-17 446798725_87912766

    #晚期实体瘤#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=961878, encodeId=42639618e820, content=<a href='/topic/show?id=d12d1042620a' target=_blank style='color:#2F92EE;'>#Br J Cancer#</a>点击查看更多相关话题 或评论点击插入您喜欢的话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=104262, encryptionId=d12d1042620a, topicName=Br J Cancer)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20221103/2796e00c9b4549e3b313ed9e7accc68f/b52d6d98bbe04782b5a4e2dd1ee80be2.jpeg, createdBy=078e1614372, createdName=MedSciZeng, createdTime=Fri Apr 30 17:23:34 CST 2021, time=2021-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1898190, encodeId=31db189819044, content=<a href='/topic/show?id=8904158e9e7' target=_blank style='color:#2F92EE;'>#SAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15879, encryptionId=8904158e9e7, topicName=SAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30f5146, createdName=zz70, createdTime=Thu Feb 04 12:27:48 CST 2021, time=2021-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886230, encodeId=79658862304d, content=Sapanisertib显示出可控的安全性，且在肾细胞癌和子宫内膜癌中观察到初步的抗肿瘤活性。, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=qinqiyun, createdTime=Thu Sep 17 23:52:10 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338223, encodeId=c812133822335, content=<a href='/topic/show?id=cd2a262068' target=_blank style='color:#2F92EE;'>#APA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2620, encryptionId=cd2a262068, topicName=APA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ce072500140, createdName=12498b3em08(暂无昵称), createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1443150, encodeId=747214431505e, content=<a href='/topic/show?id=feee598219f' target=_blank style='color:#2F92EE;'>#晚期实体瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59821, encryptionId=feee598219f, topicName=晚期实体瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55065029738, createdName=446798725_87912766, createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885664, encodeId=73558856645c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Wed Sep 16 08:19:15 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885573, encodeId=123a8855e3ec, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Tue Sep 15 21:58:58 CST 2020, time=2020-09-15, status=1, ipAttribution=)]
    2020-09-16 14818eb4m67暂无昵称

    学习

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=961878, encodeId=42639618e820, content=<a href='/topic/show?id=d12d1042620a' target=_blank style='color:#2F92EE;'>#Br J Cancer#</a>点击查看更多相关话题 或评论点击插入您喜欢的话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=104262, encryptionId=d12d1042620a, topicName=Br J Cancer)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20221103/2796e00c9b4549e3b313ed9e7accc68f/b52d6d98bbe04782b5a4e2dd1ee80be2.jpeg, createdBy=078e1614372, createdName=MedSciZeng, createdTime=Fri Apr 30 17:23:34 CST 2021, time=2021-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1898190, encodeId=31db189819044, content=<a href='/topic/show?id=8904158e9e7' target=_blank style='color:#2F92EE;'>#SAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15879, encryptionId=8904158e9e7, topicName=SAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30f5146, createdName=zz70, createdTime=Thu Feb 04 12:27:48 CST 2021, time=2021-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886230, encodeId=79658862304d, content=Sapanisertib显示出可控的安全性，且在肾细胞癌和子宫内膜癌中观察到初步的抗肿瘤活性。, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=qinqiyun, createdTime=Thu Sep 17 23:52:10 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338223, encodeId=c812133822335, content=<a href='/topic/show?id=cd2a262068' target=_blank style='color:#2F92EE;'>#APA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2620, encryptionId=cd2a262068, topicName=APA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ce072500140, createdName=12498b3em08(暂无昵称), createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1443150, encodeId=747214431505e, content=<a href='/topic/show?id=feee598219f' target=_blank style='color:#2F92EE;'>#晚期实体瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59821, encryptionId=feee598219f, topicName=晚期实体瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55065029738, createdName=446798725_87912766, createdTime=Thu Sep 17 12:27:48 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885664, encodeId=73558856645c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Wed Sep 16 08:19:15 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885573, encodeId=123a8855e3ec, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Tue Sep 15 21:58:58 CST 2020, time=2020-09-15, status=1, ipAttribution=)]
    2020-09-15 wxl882001

    了解

    0

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