Clin Cancer Res:联合抑制Gα和MEK可明显提高葡萄膜黑色素瘤的治疗效果

2021-02-03 MedSci原创 MedSci原创

联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略

所有葡萄膜黑色素瘤和部分其他黑色素瘤亚型都是由Gαq通路激活所驱动的。尽管我们已在该病的发病机制中的关键驱动信号通路的分子理解方面取得了长足的进展,但对这些黑色素瘤开展靶向治疗仍很困难。Gαq抑制剂已显示出了良好的临床前效果,但它们在不同的Gαq突变环境中的治疗活性千差万别。

Hitchman等人采用等基因黑色素细胞系统来系统地检测在人葡萄膜黑色素瘤GNAQ和CYSLTR2基因中发现的热点突变(如GNAQ: G48V、R183Q、Q209L)和(CYSLTR2: L129Q)。该细胞系统和人葡萄膜黑色素瘤细胞系被用于异种移植研究,以评估单Gαq抑制以及联合MEK抑制的治疗活性。

YM-254890对不同突变体细胞活性的抑制作用

研究结果证明,q抑制剂YM-254890在所有突变体中都能抑制下游信号,抑制细胞生长。在体内,YM-254890可以减缓肿瘤生长,但不会导致人葡萄膜黑色素瘤移植瘤的消退。

YM-254890治疗可明显缩小肿瘤体积

通过综合转录组分析,研究人员观察到,YM-254890对MAPK信号转导通路的抑制作用可持续24小时;YM-254890与一种MEK抑制剂联合作用可持续抑制MAPK信号转导通路。此外,YM-254890和MEK抑制剂联合应用还可协同抑制肿瘤生长,并使肿瘤体积缩小。

YM-254890和MEK抑制剂联合应用可进一步缩小肿瘤体积

总而言之,该研究结果表明,联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略,并扩展了广泛靶向Gαq的治疗时间窗。

原始出处:

Hitchman Tyler D,Bayshtok Gabriella,Ceraudo Emilie et al. Combined Inhibition of Gα and MEK Enhances Therapeutic Efficacy in Uveal Melanoma. Clin Cancer Res, 2020, undefined: undefined.

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    2021-05-22 sunylz
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    2021-03-22 naiwu77
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objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
  5. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
  6. 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objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
  7. 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objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Fri Feb 05 06:57:34 CST 2021, time=2021-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922607, encodeId=499e92260e0d, content=,Gαq抑制剂YM-254890在所有突变体中都能抑制下游信号,抑制细胞生长。, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:59:12 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922587, encodeId=2ddf92258e99, content=该研究结果表明,联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略,并扩展了广泛靶向Gαq的治疗时间窗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
    2021-02-03 Aidy

    ,Gαq抑制剂YM-254890在所有突变体中都能抑制下游信号,抑制细胞生长。

    0

  8. 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objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
    2021-02-03 Aidy

    该研究结果表明,联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略,并扩展了广泛靶向Gαq的治疗时间窗。

    0

  9. 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objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Fri Feb 05 06:57:34 CST 2021, time=2021-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922607, encodeId=499e92260e0d, content=,Gαq抑制剂YM-254890在所有突变体中都能抑制下游信号,抑制细胞生长。, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:59:12 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922587, encodeId=2ddf92258e99, content=该研究结果表明,联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略,并扩展了广泛靶向Gαq的治疗时间窗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
    2021-02-03 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

  10. 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objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Fri Feb 05 06:57:34 CST 2021, time=2021-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922607, encodeId=499e92260e0d, content=,Gαq抑制剂YM-254890在所有突变体中都能抑制下游信号,抑制细胞生长。, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:59:12 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=922587, encodeId=2ddf92258e99, content=该研究结果表明,联合抑制Gαq和MEK为葡萄膜黑色素瘤提供了一种很有前景的治疗策略,并扩展了广泛靶向Gαq的治疗时间窗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8585442638, createdName=Aidy, createdTime=Wed Feb 03 22:39:13 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032786, encodeId=e5261032e8620, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047274, encodeId=f8a7104e27449, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Feb 03 18:57:34 CST 2021, time=2021-02-03, status=1, ipAttribution=)]
    2021-02-03 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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