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CLIN CANCER RES：克服侵袭性B细胞淋巴瘤Venetoclax耐药策略

2018-08-30 MedSci MedSci原创

侵袭性B细胞淋巴瘤Venetoclax耐药治疗策略
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BCL-2是一种抗凋亡蛋白，在B细胞淋巴瘤中常存在异常，促进肿瘤细胞存活。近期的一项应用BCL-2抑制剂Venetoclax治疗非霍奇金淋巴瘤的临床试验表明总缓解率为44%。CLIN CANCER RES近期发表了一篇文章，研究Venetoclax治疗侵袭性B细胞淋巴瘤（包括套细胞淋巴瘤MCL和弥漫大B细胞淋巴瘤DLBCL）的生物学效应及机制。

BCL-2是一种抗凋亡蛋白，在B细胞淋巴瘤中常存在异常，促进肿瘤细胞存活。近期的一项应用BCL-2抑制剂Venetoclax治疗非霍奇金淋巴瘤的临床试验表明总缓解率为44%。CLIN CANCER RES近期发表了一篇文章，研究Venetoclax治疗侵袭性B细胞淋巴瘤（包括套细胞淋巴瘤MCL和弥漫大B细胞淋巴瘤DLBCL）的生物学效应及机制。

作者使用MCL及DLBCL细胞系，病人样本以及PDX模型研究Venetoclax有效性。使用蛋白质组学及Western blot研究Venetoclax反应机制及耐药机制。研究发现了Venetoclax活性有关的潜在生物学标志以及可以增强Venetoclax反应的联合策略。表达高水平BCL-2的细胞系、肿瘤样本及PDX模型对Venetoclax治疗极其敏感。蛋白质组学分析表明Venetoclax会改变与细胞进展有关蛋白的表达水平和磷酸化状态。短期和长期Venetoclax暴露抑制PTEN表达，导致AKT通路活性增强以及相伴的对PI3K/AKT抑制敏感。Venetoclax耐药的细胞AKT活化增强且对PI3K/AKT抑制敏感。

文章最后认为，该研究为通过PI3K/AKT抑制克服Venetoclax耐药提供了机制证据。

原始出处：
Lan V Pham,Shengjian Huang,et al.Strategic Treatment Targeting to Overcome Venetoclax Resistance in Aggressive B-cell Lymphomas.CLIN CANCER RES.August 2018 doi:10.1158/1078-0432.CCR-17-3004

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    2019-02-17 canlab

    #NET#

    0

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    2019-02-24 klivis

    #Venetoclax耐药#

    0

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    2018-09-10 zhu_jun9837

    #侵袭性B细胞淋巴瘤#

    0

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    2018-09-03 marlenexl

    #细胞淋巴瘤#

    0

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    2018-09-01 xiaoyeshuang

    #B细胞#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1734053, encodeId=57b21e340536b, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Sun Feb 17 13:23:00 CST 2019, time=2019-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1690742, encodeId=873e1690e42e2, content=<a href='/topic/show?id=7bbd183e8e5' target=_blank style='color:#2F92EE;'>#Venetoclax耐药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18378, encryptionId=7bbd183e8e5, topicName=Venetoclax耐药)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b05229113026, createdName=klivis, createdTime=Sun Feb 24 00:23:00 CST 2019, time=2019-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2070911, encodeId=80c520e091157, content=<a href='/topic/show?id=82b0269997f' target=_blank style='color:#2F92EE;'>#侵袭性B细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26999, encryptionId=82b0269997f, topicName=侵袭性B细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3609256, createdName=zhu_jun9837, createdTime=Mon Sep 10 14:23:00 CST 2018, time=2018-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702512, encodeId=edd41e02512f7, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Mon Sep 03 09:23:00 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273261, encodeId=278512e326128, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Sat Sep 01 10:23:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1366316, encodeId=8c11136631636, content=<a href='/topic/show?id=186126998e2' target=_blank style='color:#2F92EE;'>#侵袭性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26998, encryptionId=186126998e2, topicName=侵袭性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Sat Sep 01 10:23:00 CST 2018, time=2018-09-01, status=1, ipAttribution=)]
    2018-09-01 sunyl07

    #侵袭性#

    0