CLIN CANCER RES：PI3K和CDK4/6联合抑制治疗PIK3CA突变肺鳞状细胞癌

2018-12-19 MedSci MedSci原创

肺鳞状细胞癌（LUSC）是非小细胞肺癌的主要亚型，其特征是存在多种遗传改变，特别PI3K通路改变，在超过50％的LUSC病例中得到证实。尽管是具有治疗前景的靶点，单一药物PI3K抑制剂在LUSC中表现的治疗效果一般。因此需要靶向LUSC的新型组合疗法。CLIN CANCER RES近期发表了一篇文章研究这一问题。

肺鳞状细胞癌（LUSC）是非小细胞肺癌的主要亚型，其特征是存在多种遗传改变，特别PI3K通路改变，在超过50％的LUSC病例中得到证实。尽管是具有治疗前景的靶点，单一药物PI3K抑制剂在LUSC中表现的治疗效果一般。因此需要靶向LUSC的新型组合疗法。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者在LUSC患者的异种移植模型（PDX）中评估PI3K抑制剂单独和与CDK4/6抑制剂联合的治疗效果。还进行了药效学研究以确认化合物的靶向抑制效果。研究结果表明，与LUSC的癌症基因组图谱分析的结果一致，研究中的LUSC PDX模型基因组谱分析发现超过50％的模型中存在PI3K通路改变。在12模型中使用PI3K抑制剂发现PIK3CA突变鉴定是治疗反应的预测标志。与单药治疗相比，在PIK3CA突变的模型中使用PI3K和CDK4/6的联合抑制抗肿瘤效果更明显。此外，两种药物的组合可以达到对PI3K和细胞周期途径的靶向抑制。

文章最后认为，PIK3CA突变可预测LUSC对PI3K抑制剂的反应。PI3K和CDK4/6联合抑制可以增强治疗效果。这些发现为PI3K和CDK4/6联合抑制剂治疗PIK3CA -mutant LUSC的临床试验提供了证据。

原始出处：

Ruoshi Shi, Ming Li, et al. Targeting the CDK4/6-Rb Pathway Enhances Response to PI3K Inhibition in PIK3CA-Mutant Lung Squamous Cell Carcinoma. CLIN CANCER RES. December 2018 doi: 10.1158/1078-0432.CCR-18-0717

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2019-09-11 仁者大医

#细胞癌#

36 0
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2019-10-08 xinmeili

#PIK3CA#

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2019-07-28 soongzhihua

#CDK4#

29 0
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2019-08-25 ms6323715314570549

#PIK3CA突变#

24 0
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2019-08-26 zsyan

#肺鳞状细胞癌#

26 0
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2018-12-21 ms1292405679162969

#PI3K#

28 0
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2018-12-21 zhouqu_8

#CDK#

29 0
[GetPortalCommentsPageByObjectIdResponse(id=1978781, encodeId=6b3d19e8781a3, 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=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Wed Sep 11 12:00:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007517, encodeId=bb5b200e51725, content=<a href='/topic/show?id=fe2b142e95c' target=_blank style='color:#2F92EE;'>#PIK3CA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14279, encryptionId=fe2b142e95c, topicName=PIK3CA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Tue Oct 08 02:00:00 CST 2019, time=2019-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703085, encodeId=dba21e03085dc, content=<a href='/topic/show?id=98b24402bb' target=_blank style='color:#2F92EE;'>#CDK4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4402, encryptionId=98b24402bb, topicName=CDK4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=166330479856, createdName=soongzhihua, createdTime=Sun Jul 28 02:00:00 CST 2019, time=2019-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710576, encodeId=27971e10576cc, content=<a href='/topic/show?id=4ad0142806f' target=_blank style='color:#2F92EE;'>#PIK3CA突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14280, encryptionId=4ad0142806f, topicName=PIK3CA突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=617b31881621, createdName=ms6323715314570549, createdTime=Sun Aug 25 11:00:00 CST 2019, time=2019-08-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1672089, encodeId=541916e20895d, content=<a href='/topic/show?id=2eb682395fd' target=_blank style='color:#2F92EE;'>#肺鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82395, encryptionId=2eb682395fd, topicName=肺鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfc26872821, createdName=zsyan, createdTime=Mon Aug 26 14:00:00 CST 2019, time=2019-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333206, encodeId=0b5d13332068c, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, 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 02:00:00 CST 2018, time=2018-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435511, encodeId=2abe1435511cb, content=<a href='/topic/show?id=09dc439915' target=_blank style='color:#2F92EE;'>#CDK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4399, encryptionId=09dc439915, topicName=CDK)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Dec 21 02:00:00 CST 2018, time=2018-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1490688, encodeId=1be21490688aa, content=<a href='/topic/show?id=2765440372' target=_blank style='color:#2F92EE;'>#CDK4/6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4403, encryptionId=2765440372, topicName=CDK4/6)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c7068807080, createdName=zhangj7111, createdTime=Fri Dec 21 02:00:00 CST 2018, time=2018-12-21, status=1, ipAttribution=)]
2018-12-21 zhangj7111

#CDK4/6#

29 0

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