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CLIN CANCER RES：靶向TFE3/IRS-1/PI3K/mTOR轴治疗易位肾细胞癌

2018-12-19 MedSci MedSci原创

易位肾细胞癌TFE3mTOR
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易位肾细胞癌（tRCC）是一种罕见的肾癌亚型，与TFE3，TFEB或MITF基因融合有关，对RCC的标准治疗无反应。因此，需要寻找新的治疗靶标。CLIN CANCER RES近期发表了一篇文章研究这一问题。

易位肾细胞癌（tRCC）是一种罕见的肾癌亚型，与TFE3，TFEB或MITF基因融合有关，对RCC的标准治疗无反应。因此，需要寻找新的治疗靶标。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者建立了tRCC患者来源的异种移植模型RP-R07，作为应用二代测序和生物信息学分析进行药物开发的临床前模型。然后使用体外和体内模型评估抑制靶向信号通路的治疗效果。研究结果发现，通过RNA-seq发现SFPQ-TFE3融合的存在，并通过RT-PCR得到验证。TFE3染色质免疫沉淀联合深度测序分析发现RP-R07模型中PI3K/AKT/mTOR通路富集。miRNA芯片也发现PI3K/AKT/mTOR是RP-R07模型中的高度富集通路。与透明细胞RCC细胞相比，tRCC细胞系中磷酸-S6和磷酸-4EBP1表达更高，TFE3-tRCC模型中PI3/AKT/mTOR通路也出现上调。与单节点抑制相比，PI3K/AKT和mTOR轴的多点靶向抗增殖效果更明显。RP-R07模型中敲低TFE3导致IRS-1的表达降低并抑制细胞增殖。

文章最后认为，TFE3/IRS-1/PI3K/AKT/mTOR可能是TFE3-tRCC中的异常通路。对TFE3-tRCC患者使用双重PI3K/mTOR抑制剂具有治疗潜力。

原始出处：

Nur P. Damayanti, Justin A. Budka, et al. Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma. CLIN CANCER RES. December 2018 doi: 10.1158/1078-0432.CCR-18-0269

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1978780, encodeId=517f19e87805e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Tue Apr 23 18:42:00 CST 2019, time=2019-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333205, encodeId=068b1333205a2, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14231, encryptionId=ecfa1423117, topicName=PI3K)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477865, encodeId=f2b914e7865de, content=<a href='/topic/show?id=944315e85c0' target=_blank style='color:#2F92EE;'>#S-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15785, encryptionId=944315e85c0, topicName=S-1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6477383481, createdName=ms3117646317107274, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=)]
    2019-04-23 qingting

    #细胞癌#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1978780, encodeId=517f19e87805e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Tue Apr 23 18:42:00 CST 2019, time=2019-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333205, encodeId=068b1333205a2, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14231, encryptionId=ecfa1423117, topicName=PI3K)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477865, encodeId=f2b914e7865de, content=<a href='/topic/show?id=944315e85c0' target=_blank style='color:#2F92EE;'>#S-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15785, encryptionId=944315e85c0, topicName=S-1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6477383481, createdName=ms3117646317107274, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=)]
    2018-12-21 ms1292405679162969

    #PI3K#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1978780, encodeId=517f19e87805e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Tue Apr 23 18:42:00 CST 2019, time=2019-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333205, encodeId=068b1333205a2, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14231, encryptionId=ecfa1423117, topicName=PI3K)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477865, encodeId=f2b914e7865de, content=<a href='/topic/show?id=944315e85c0' target=_blank style='color:#2F92EE;'>#S-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15785, encryptionId=944315e85c0, topicName=S-1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6477383481, createdName=ms3117646317107274, createdTime=Fri Dec 21 01:42:00 CST 2018, time=2018-12-21, status=1, ipAttribution=)]
    2018-12-21 ms3117646317107274

    #S-1#

    0

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