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中国表皮生长因子受体基因突变和间变淋巴瘤激酶融合基因阳性非小细胞肺癌诊断治疗指南(2013版)

2014-02-06 MedSci MedSci原创

肺癌的发病率和死亡率均居我国恶性肿瘤第1位,其中80%~85%的病例为非小细胞肺癌(non-small cell lung cancer,NSCLC)。NSCLC患者的5年生存率约为15%,约70%的NSCLC患者确诊时即为晚期。基于分子靶点的个体化分子靶向治疗成为目前NSCLC研究中的热点,尤其是以表皮生长因子受体(epidermal growth factor

肺癌的发病率和死亡率均居我国恶性肿瘤第1位,其中80%~85%的病例为非小细胞肺癌(non-small cell lung cancer,NSCLC)。NSCLC患者的5年生存率约为15%,约70%的NSCLC患者确诊时即为晚期。基于分子靶点的个体化分子靶向治疗成为目前NSCLC研究中的热点,尤其是以表皮生长因子受体(epidermal growth factor receptor,EGFR)和间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)为靶点药物的发现,在NSCLC个体化治疗的发展中具有里程碑式的意义。

EGFR是一种跨膜受体,与细胞增殖、转移、凋亡等多种信号传导通路相关。EGFR突变主要包括4种类型:外显子19缺失突变、外显子21点突变、外显子18点突变以及外显子20插入突变。最常见的EGFR突变为外显子19 LREA缺失和外显子21 L858R突变,二者均会导致酪氨酸激酶结构域活化,且均为EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)的敏感性突变。外显子20的T790M突变与EGFR-TKI的获得性耐药有关,还有许多类型的突变临床意义尚不明确。肺腺癌患者的EGFR突变率在高加索人群中约为10%。在2012年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)年会上报告了PIONEER研究的结果,这项针对亚裔晚期肺腺癌患者的前瞻性流行病学研究显示,中国晚期肺腺癌患者的EGFR突变率为50.2%。

ALK最早是在间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的一个亚型中被发现,并因此得名。继2007年Soda等首次报道了在NSCLC中发现染色体2p的倒位,造成棘皮动物微管相关类蛋白4(echinoderm microtubule-associated proteinlike 4,EMIA)的N-端与ALK的激酶区融合产生一个融合基因之后,一系列研究显示,EMI4-ALK倒位有多种变异,且均可导致具有催化活性的激酶融合蛋白变异体的表达,而动物实验证实该激酶具有致癌性。EMI4-ALK融合基因阳性的NSCLC患者已经被定义为NSCLC的另一种特殊疾病亚型。国外研究显示,在NSCLC患者中,ALK融合基因阳性的发生率约为5%。国内学者报道,中国NSCLC患者ALK的阳性率约为3%一11%。

已有多项临床研究证明,EGFR-TKI和ALK抑制剂能分别使EGFR突变和ALK融合基因阳性的NSCLC患者显著获益。EGFR-TKI吉非替尼、厄洛替尼、埃克替尼和ALK抑制剂克唑替尼相继于2005年2月25日、2007年3月17日、2011年6月7日和2013年1月22日经中国食品与药品监督管理局(State Food and Drug Administration,SFDA)批准上市,为改善晚期NSCLC患者的生存带来新的契机。

在NSCLC患者中检测EGFR、ALK基因状态具有重要的临床意义,美国、欧盟的权威学术机构都已制订出各自的检测和治疗指南。为了提高我国在该领域诊断和治疗的规范化水平,中国医师协会肿瘤医师分会和中国抗癌协会肿瘤临床化疗专业委员会组织专家们制订了《中国表皮生长因子受体基因突变和间变淋巴瘤激酶融合基因阳性非小细胞肺癌诊断治疗指南》,从EGFR基因突变检测、EGFR突变阳性NSCLC患者治疗、ALK融合基因检测、ALK融合基因阳性NSCLC患者治疗四方面进行系统介绍,旨在提高我国在该领域的规范化诊治水平。


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  7. 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createdAvatar=null, createdBy=443c38859879, createdName=cqlidoudou, createdTime=Wed Dec 17 08:22:00 CST 2014, time=2014-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045820, encodeId=86a620458206e, content=<a href='/topic/show?id=ecf49e5173d' target=_blank style='color:#2F92EE;'>#阳性非小细胞肺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97517, encryptionId=ecf49e5173d, topicName=阳性非小细胞肺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a19115, createdName=stfoxst, createdTime=Wed Jan 14 07:22:00 CST 2015, time=2015-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059455, encodeId=d30120594552d, 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=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 04 20:22:00 CST 2014, time=2014-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776758, encodeId=4c021e7675893, content=<a href='/topic/show?id=1845902317a' target=_blank style='color:#2F92EE;'>#表皮生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90231, encryptionId=1845902317a, topicName=表皮生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7fe639008353, createdName=chentianping, createdTime=Wed Dec 24 05:22:00 CST 2014, time=2014-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423616, encodeId=20da1423616c4, content=<a href='/topic/show?id=9ece91631bd' target=_blank style='color:#2F92EE;'>#诊断治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91631, encryptionId=9ece91631bd, topicName=诊断治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5afb3820115, createdName=feifers, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495924, encodeId=4e9914959245e, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517939, encodeId=e958151e939a4, content=<a href='/topic/show?id=aa2269613cd' target=_blank style='color:#2F92EE;'>#生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69613, encryptionId=aa2269613cd, topicName=生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3df311117154, createdName=12499e01m50暂无昵称, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525385, encodeId=3730152538550, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1542618, encodeId=a4ff154261892, content=<a href='/topic/show?id=fcec88861b1' target=_blank style='color:#2F92EE;'>#融合基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88861, encryptionId=fcec88861b1, topicName=融合基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=886613418495, createdName=ms3153534357578991, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=)]
    2014-02-08 redcrab
  8. [GetPortalCommentsPageByObjectIdResponse(id=1663620, encodeId=e0dd1663620d5, content=<a href='/topic/show?id=84c4902325a' target=_blank style='color:#2F92EE;'>#表皮生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90232, encryptionId=84c4902325a, topicName=表皮生长因子受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a88a25636997, createdName=ms9608593228839890, createdTime=Sun Jan 04 20:22:00 CST 2015, time=2015-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776007, encodeId=93231e760077d, content=<a href='/topic/show?id=b98d69614ae' target=_blank style='color:#2F92EE;'>#生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69614, encryptionId=b98d69614ae, topicName=生长因子受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=443c38859879, createdName=cqlidoudou, createdTime=Wed Dec 17 08:22:00 CST 2014, time=2014-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045820, encodeId=86a620458206e, content=<a href='/topic/show?id=ecf49e5173d' target=_blank style='color:#2F92EE;'>#阳性非小细胞肺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97517, encryptionId=ecf49e5173d, topicName=阳性非小细胞肺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a19115, createdName=stfoxst, createdTime=Wed Jan 14 07:22:00 CST 2015, time=2015-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059455, encodeId=d30120594552d, 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=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 04 20:22:00 CST 2014, time=2014-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776758, encodeId=4c021e7675893, content=<a href='/topic/show?id=1845902317a' target=_blank style='color:#2F92EE;'>#表皮生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90231, encryptionId=1845902317a, topicName=表皮生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7fe639008353, createdName=chentianping, createdTime=Wed Dec 24 05:22:00 CST 2014, time=2014-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423616, encodeId=20da1423616c4, content=<a href='/topic/show?id=9ece91631bd' target=_blank style='color:#2F92EE;'>#诊断治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91631, encryptionId=9ece91631bd, topicName=诊断治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5afb3820115, createdName=feifers, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495924, encodeId=4e9914959245e, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517939, encodeId=e958151e939a4, content=<a href='/topic/show?id=aa2269613cd' target=_blank style='color:#2F92EE;'>#生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69613, encryptionId=aa2269613cd, topicName=生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3df311117154, createdName=12499e01m50暂无昵称, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525385, encodeId=3730152538550, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1542618, encodeId=a4ff154261892, content=<a href='/topic/show?id=fcec88861b1' target=_blank style='color:#2F92EE;'>#融合基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88861, encryptionId=fcec88861b1, topicName=融合基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=886613418495, createdName=ms3153534357578991, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1663620, encodeId=e0dd1663620d5, content=<a href='/topic/show?id=84c4902325a' target=_blank style='color:#2F92EE;'>#表皮生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90232, encryptionId=84c4902325a, topicName=表皮生长因子受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a88a25636997, createdName=ms9608593228839890, createdTime=Sun Jan 04 20:22:00 CST 2015, time=2015-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776007, encodeId=93231e760077d, content=<a href='/topic/show?id=b98d69614ae' target=_blank style='color:#2F92EE;'>#生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69614, encryptionId=b98d69614ae, topicName=生长因子受体)], attachment=null, authenticateStatus=null, 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style='color:#2F92EE;'>#诊断治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91631, encryptionId=9ece91631bd, topicName=诊断治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5afb3820115, createdName=feifers, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495924, encodeId=4e9914959245e, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517939, encodeId=e958151e939a4, content=<a href='/topic/show?id=aa2269613cd' target=_blank style='color:#2F92EE;'>#生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69613, encryptionId=aa2269613cd, topicName=生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3df311117154, createdName=12499e01m50暂无昵称, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525385, encodeId=3730152538550, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1542618, encodeId=a4ff154261892, content=<a href='/topic/show?id=fcec88861b1' target=_blank style='color:#2F92EE;'>#融合基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88861, encryptionId=fcec88861b1, topicName=融合基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=886613418495, createdName=ms3153534357578991, createdTime=Sat Feb 08 07:22:00 CST 2014, time=2014-02-08, status=1, ipAttribution=)]
    2014-02-08 licz0427
  10. [GetPortalCommentsPageByObjectIdResponse(id=1663620, encodeId=e0dd1663620d5, content=<a href='/topic/show?id=84c4902325a' target=_blank style='color:#2F92EE;'>#表皮生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90232, encryptionId=84c4902325a, topicName=表皮生长因子受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a88a25636997, createdName=ms9608593228839890, createdTime=Sun Jan 04 20:22:00 CST 2015, time=2015-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776007, encodeId=93231e760077d, content=<a href='/topic/show?id=b98d69614ae' target=_blank style='color:#2F92EE;'>#生长因子受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69614, encryptionId=b98d69614ae, topicName=生长因子受体)], attachment=null, authenticateStatus=null, 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