MOL CANCER THER:非小细胞肺癌细胞对EGFR -酪氨酸激酶抑制剂埃罗替尼的敏感性

2017-05-29 MedSci MedSci原创

EGFR-TKI 在EGFR突变的非小细胞肺癌细胞中的治疗效果已有广泛研究,但是其在野生型EGFR肿瘤中的治疗作用微乎其微在临床应用也被限制。 第一代和第二代EGFR-TKIs相继应用于临床治疗,但是大部分患者治疗一段时间后会出现EGFR T790M突变而导致获得性耐药。而靶向EGFR T790M耐药突变的第三代EGFR-TKIs目前已进入临床研究。

近日,国际杂志Molecular Cancer Therapeutics上在线发表一项关于表皮生长因子受体(EGFR)酪氨酸酶抑制剂(EGFR-TKI)在治疗EGFR突变的晚期非小细胞肺癌NSCLC)的作用的研究。

EGFR-TKI EGFR突变的非小细胞肺癌细胞中的治疗效果已有广泛研究,但是其在野生型EGFR肿瘤中的治疗作用微乎其微在临床应用也被限制。 第一代和第二代EGFR-TKIs相继应用于临床治疗,但是大部分患者治疗一段时间后会出现EGFR T790M突变而导致获得性耐药。而靶向EGFR T790M耐药突变的第三代EGFR-TKIs目前已进入临床研究。

研究人员在体内实验采用了PDX模型,即人源性肿瘤组织异种移植模型,这一模型是将取自病人的小块肿瘤组织植入实验小鼠体内,模拟其原来的生长环境,最大程度的保留肿瘤自身的特征。该模型具有较高的瘤内异质性和分子多样性,使得这一模型是目前最接近人体实际情况的模型。此外,研究人员发现发现病人对顺铂预处理呈现不同的响应。

研究提出了一系列的marker以区分埃罗替尼敏感型和非敏感型肿瘤。这些marker对于以埃罗替尼维持治疗的病人是有益的。

原始出处:

Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, et.al. Sensitization of EGFR wild-type non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitor erlotinib.

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  5. 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  6. 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    2017-06-11 189****7206

    学习了谢谢分享。

    0

  7. 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GetPortalCommentsPageByObjectIdResponse(id=207828, encodeId=cbed20e82838, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Wed Jun 07 21:01:00 CST 2017, time=2017-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=206973, encodeId=4e372069e336, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=08bb2061153, createdName=189****7206, createdTime=Mon Jun 05 22:25:58 CST 2017, time=2017-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=205529, encodeId=a59920552957, content=学习了,是什么样的marker?, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuEYA6ZJS2RZEJp0LgvdXH072EszfvD8xib0UGViaFO626UZIkB4ibvY1NicVJDFUSYoQjZvL6gnjziaYl/0, createdBy=48511932758, createdName=1e0d2fb7m34(暂无匿称), createdTime=Fri Jun 02 08:29:52 CST 2017, time=2017-06-02, status=1, ipAttribution=)]
    2017-06-09 130****4638

    学习了谢谢分享。

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=2039866, encodeId=acb42039866cd, content=<a href='/topic/show?id=f7526685963' target=_blank style='color:#2F92EE;'>#激酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66859, encryptionId=f7526685963, topicName=激酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Nov 03 10:19:00 CST 2017, time=2017-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851439, encodeId=a6dd18514394d, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Mar 31 17:19:00 CST 2018, time=2018-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069801, encodeId=0332206980181, content=<a href='/topic/show?id=904282239db' target=_blank style='color:#2F92EE;'>#肺癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82239, encryptionId=904282239db, topicName=肺癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c77e138, createdName=kalseyzl, createdTime=Tue Jul 18 11:19:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059606, encodeId=3ed820596066b, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Tue Mar 06 16:19:00 CST 2018, time=2018-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1740631, encodeId=f9e41e4063199, content=<a href='/topic/show?id=fd0a95511dd' target=_blank style='color:#2F92EE;'>#酪氨酸激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95511, encryptionId=fd0a95511dd, topicName=酪氨酸激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=22af34798690, createdName=luckyshitiancai_42705695, createdTime=Wed Jan 03 11:19:00 CST 2018, time=2018-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=209292, encodeId=f61b209292db, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=08bb2061153, createdName=189****7206, createdTime=Sun Jun 11 08:21:16 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=208454, encodeId=d85f208454c2, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Fri Jun 09 07:15:49 CST 2017, time=2017-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=207828, encodeId=cbed20e82838, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Wed Jun 07 21:01:00 CST 2017, time=2017-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=206973, encodeId=4e372069e336, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=08bb2061153, createdName=189****7206, createdTime=Mon Jun 05 22:25:58 CST 2017, time=2017-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=205529, encodeId=a59920552957, content=学习了,是什么样的marker?, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuEYA6ZJS2RZEJp0LgvdXH072EszfvD8xib0UGViaFO626UZIkB4ibvY1NicVJDFUSYoQjZvL6gnjziaYl/0, createdBy=48511932758, createdName=1e0d2fb7m34(暂无匿称), createdTime=Fri Jun 02 08:29:52 CST 2017, time=2017-06-02, status=1, ipAttribution=)]
    2017-06-07 130****4638

    学习了谢谢分享。

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=2039866, encodeId=acb42039866cd, content=<a href='/topic/show?id=f7526685963' target=_blank style='color:#2F92EE;'>#激酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66859, encryptionId=f7526685963, topicName=激酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Nov 03 10:19:00 CST 2017, time=2017-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851439, encodeId=a6dd18514394d, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Mar 31 17:19:00 CST 2018, time=2018-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069801, encodeId=0332206980181, content=<a href='/topic/show?id=904282239db' target=_blank style='color:#2F92EE;'>#肺癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82239, encryptionId=904282239db, topicName=肺癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c77e138, createdName=kalseyzl, createdTime=Tue Jul 18 11:19:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059606, encodeId=3ed820596066b, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Tue Mar 06 16:19:00 CST 2018, time=2018-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1740631, encodeId=f9e41e4063199, content=<a href='/topic/show?id=fd0a95511dd' target=_blank style='color:#2F92EE;'>#酪氨酸激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95511, encryptionId=fd0a95511dd, topicName=酪氨酸激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=22af34798690, createdName=luckyshitiancai_42705695, createdTime=Wed Jan 03 11:19:00 CST 2018, time=2018-01-03, status=1, ipAttribution=), 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GetPortalCommentsPageByObjectIdResponse(id=207828, encodeId=cbed20e82838, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Wed Jun 07 21:01:00 CST 2017, time=2017-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=206973, encodeId=4e372069e336, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=08bb2061153, createdName=189****7206, createdTime=Mon Jun 05 22:25:58 CST 2017, time=2017-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=205529, encodeId=a59920552957, content=学习了,是什么样的marker?, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuEYA6ZJS2RZEJp0LgvdXH072EszfvD8xib0UGViaFO626UZIkB4ibvY1NicVJDFUSYoQjZvL6gnjziaYl/0, createdBy=48511932758, createdName=1e0d2fb7m34(暂无匿称), createdTime=Fri Jun 02 08:29:52 CST 2017, time=2017-06-02, status=1, ipAttribution=)]
    2017-06-05 189****7206

    学习了谢谢分享。

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=2039866, encodeId=acb42039866cd, content=<a href='/topic/show?id=f7526685963' target=_blank style='color:#2F92EE;'>#激酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66859, encryptionId=f7526685963, topicName=激酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Nov 03 10:19:00 CST 2017, time=2017-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851439, encodeId=a6dd18514394d, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Tue Mar 06 16:19:00 CST 2018, time=2018-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1740631, encodeId=f9e41e4063199, content=<a href='/topic/show?id=fd0a95511dd' target=_blank style='color:#2F92EE;'>#酪氨酸激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95511, encryptionId=fd0a95511dd, topicName=酪氨酸激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=22af34798690, createdName=luckyshitiancai_42705695, createdTime=Wed Jan 03 11:19:00 CST 2018, time=2018-01-03, status=1, ipAttribution=), 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GetPortalCommentsPageByObjectIdResponse(id=207828, encodeId=cbed20e82838, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Wed Jun 07 21:01:00 CST 2017, time=2017-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=206973, encodeId=4e372069e336, content=学习了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=08bb2061153, createdName=189****7206, createdTime=Mon Jun 05 22:25:58 CST 2017, time=2017-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=205529, encodeId=a59920552957, content=学习了,是什么样的marker?, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuEYA6ZJS2RZEJp0LgvdXH072EszfvD8xib0UGViaFO626UZIkB4ibvY1NicVJDFUSYoQjZvL6gnjziaYl/0, createdBy=48511932758, createdName=1e0d2fb7m34(暂无匿称), createdTime=Fri Jun 02 08:29:52 CST 2017, time=2017-06-02, status=1, ipAttribution=)]
    2017-06-02 1e0d2fb7m34(暂无匿称)

    学习了,是什么样的marker?

    0

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 每年被诊断为肺癌的患者约有20-25%的可以切除治疗的非小细胞肺癌(NSCLC)。但是,仅有六成的患者可以在术后存活超过五年。在十年前第一次有报道基于顺铂的辅助化疗可以带来显著的存活率。随后其他的随机试验也证明了NSCLC2和3期患者接受辅助化疗可以存活更久。埃罗替尼是一种口服的小分子表皮生长因子受体酪氨酸激酶抑制剂,已经被证明对晚期肺癌有效。 研究人员首先假设埃罗替尼用于N

JCO:埃罗替尼、质子泵抑制剂同服,理想再来点可乐

 埃罗替尼是一种口服酪氨酸激酶抑制剂,对于治疗非小细胞肺癌有着很好的效果。埃罗替尼口服的优势导致了一个新的相关的问题。埃罗替尼的胃肠道吸收是一个复杂的多因素导致的过程。其中影响吸收的最重要的一个因素就是胃内的pH。当埃罗替尼和质子泵抑制剂同服时,胃内pH值出现上升,直接导致了埃罗替尼生物利用度的下降。研究人员假设这两种药物的相互作用可以通过服用酸性可乐饮料逆转。 在这项随机、交

Lancet Respir Med:埃罗替尼与贝伐单抗联合用药使非小细胞肺癌T790M突变患者获益

酪氨酸激酶抑制剂埃罗替尼可改善晚期存在EGFR突变的晚期非小细胞肺癌患者结局。此前有III期临床试验BeTa研究表明,在EGFR突变患者中,埃罗替尼与贝伐单抗联合使用,中位PFS显着高于埃罗替尼单独使用组。在未接受治疗的患者中,同时存在T790M和另一种EGFR突变者的PFS(无进展生存期)短于无T790M突变者。而研究者则针对T790M突变,建立了这项概念论证研究。

EJC:培美曲塞+埃罗替尼可改善非鳞状NSCLC生存

培美曲塞和埃罗替尼已被批准用于局部晚期或转移性非小细胞肺癌(NSCLC)患者二线治疗。美国礼来公司进行了一项多中心、随机、非盲、平行的II期临床试验,对培美曲塞单药及培美曲塞联合埃罗替尼用于非鳞状NSCLC患者治疗的疗效和安全性进行了评估,并于2014年4月将研究结果在线发表于《欧洲癌症杂志》(EJC)。患者入组标准为含有1处或1处以上经实体瘤疗效评价标准(RECIST)评估为可测量病灶,且美国东