Br J Cancer:Migrastatic:转移性黑色素瘤的潜在抗转移治疗药物

2021-06-30 xiaozeng MedSci原创

转移是癌症的一大标志,也是大多数癌症死亡的主要原因。

转移是癌症的一大标志,也是大多数癌症死亡的主要原因。但由于其潜在机制的复杂性以及临床终点定义的困难,也使得转移性癌症难以靶向。最近,研究人员定义了一类新型药物,Migrastatics(迁移药物)被定义为干扰所有癌细胞侵袭模式并具有干扰癌症转移能力的药物。

该药物的开发取决于批准法规的完善以及对一般毒性较低但对癌细胞扩散具有高功效的化合物的广泛筛选。临床前转移模型也极大地受益于在体内可视化癌细胞并定量跟踪其扩散以评估转移性药物的临床前功效的相应策略。

在该研究中,研究人员对公开可用的黑色素瘤数据库进行生物信息学分析。并通过体外靶标验证,开发了一种新型的可追踪自发转移性黑色素瘤模型以进行体内验证,并通过组织学实验确认肿瘤组织的药物作用。

新型Migrastatic迁移药物的临床前研发示意图

生物信息学分析结果将ROCK-myosin II通路以及该通路上的各种成分确定为黑色素瘤的潜在相关靶标。研究人员发现,RhoA上游的几个RhoGEF存在冗余,且ROCK被鉴定为RhoA下游的可药物治疗靶标。两种ROCK抑制剂的抗转移作用均通过黑色素瘤转移追踪和病理学实验得以证实。

通过癌症患者数据库确定参与黑色素瘤发生发展的基因

总而言之,该研究提出了Migrastatic药物开发的模式。研究人员采用一种新型的可追踪自发性黑色素瘤转移模型,通过非侵入性成像技术在体内量化癌症转移和药物的抗转移作用。


原始出处:

Maiques, O., Fanshawe, B., Crosas-Molist, E. et al. A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma. Br J Cancer (25 June 2021).

 

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    2022-02-16 sunylz
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[GetPortalCommentsPageByObjectIdResponse(id=1813688, encodeId=0ed1181368879, content=<a href='/topic/show?id=5f3493451ce' target=_blank style='color:#2F92EE;'>#转移治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93451, encryptionId=5f3493451ce, topicName=转移治疗)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/xkicoVBAnV4HxvdCqC1viaW8wdLQdN9hVP9icgqqDsxC6UVPjfhogdfc2iaU1xNUMVlFl5QicicWrjWQBTsVye5ngOQQ/132, createdBy=f92f2500185, createdName=ms7405317358118777, createdTime=Wed Jan 12 03:02:26 CST 2022, time=2022-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712848, encodeId=146b1e12848cd, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b9831894722, createdName=ms24272190615788285182, createdTime=Thu May 26 09:02:26 CST 2022, time=2022-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680736, encodeId=f9cb1680e360a, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Wed Feb 16 17:02:26 CST 2022, time=2022-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1952140, encodeId=2a0c19521403d, content=<a href='/topic/show?id=a641952930' target=_blank style='color:#2F92EE;'>#IGRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9529, encryptionId=a641952930, topicName=IGRA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6cc1239, createdName=sodoo, createdTime=Sun Feb 13 07:02:26 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1921836, encodeId=49cc19218368f, content=<a href='/topic/show?id=4f0a6469837' target=_blank style='color:#2F92EE;'>#治疗药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64698, encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Aug 15 03:02:26 CST 2021, time=2021-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794312, encodeId=9ae51e943123e, content=<a href='/topic/show?id=04b316e617e' target=_blank style='color:#2F92EE;'>#Stati#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16761, encryptionId=04b316e617e, topicName=Stati)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6c32257, createdName=DEXTER3139, createdTime=Wed Nov 17 02:02:26 CST 2021, time=2021-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1361581, encodeId=2196136158109, content=<a href='/topic/show?id=bcd093445b5' target=_blank style='color:#2F92EE;'>#转移性黑色素瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93445, encryptionId=bcd093445b5, topicName=转移性黑色素瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d39f177, createdName=lixiao3326, createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386783, encodeId=1f031386e83ed, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559069, encodeId=005b1559069b7, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565078, encodeId=150e15650e8f8, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=)]
    2022-02-13 sodoo
  5. [GetPortalCommentsPageByObjectIdResponse(id=1813688, encodeId=0ed1181368879, content=<a href='/topic/show?id=5f3493451ce' target=_blank style='color:#2F92EE;'>#转移治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93451, encryptionId=5f3493451ce, topicName=转移治疗)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/xkicoVBAnV4HxvdCqC1viaW8wdLQdN9hVP9icgqqDsxC6UVPjfhogdfc2iaU1xNUMVlFl5QicicWrjWQBTsVye5ngOQQ/132, createdBy=f92f2500185, createdName=ms7405317358118777, createdTime=Wed Jan 12 03:02:26 CST 2022, time=2022-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712848, encodeId=146b1e12848cd, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, 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style='color:#2F92EE;'>#IGRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9529, encryptionId=a641952930, topicName=IGRA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6cc1239, createdName=sodoo, createdTime=Sun Feb 13 07:02:26 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1921836, encodeId=49cc19218368f, content=<a href='/topic/show?id=4f0a6469837' target=_blank style='color:#2F92EE;'>#治疗药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64698, encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Aug 15 03:02:26 CST 2021, time=2021-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794312, encodeId=9ae51e943123e, content=<a href='/topic/show?id=04b316e617e' target=_blank style='color:#2F92EE;'>#Stati#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16761, encryptionId=04b316e617e, topicName=Stati)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6c32257, createdName=DEXTER3139, createdTime=Wed Nov 17 02:02:26 CST 2021, time=2021-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1361581, encodeId=2196136158109, content=<a href='/topic/show?id=bcd093445b5' target=_blank style='color:#2F92EE;'>#转移性黑色素瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93445, encryptionId=bcd093445b5, topicName=转移性黑色素瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d39f177, createdName=lixiao3326, createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386783, encodeId=1f031386e83ed, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559069, encodeId=005b1559069b7, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565078, encodeId=150e15650e8f8, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1813688, encodeId=0ed1181368879, content=<a href='/topic/show?id=5f3493451ce' target=_blank style='color:#2F92EE;'>#转移治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93451, encryptionId=5f3493451ce, topicName=转移治疗)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/xkicoVBAnV4HxvdCqC1viaW8wdLQdN9hVP9icgqqDsxC6UVPjfhogdfc2iaU1xNUMVlFl5QicicWrjWQBTsVye5ngOQQ/132, createdBy=f92f2500185, createdName=ms7405317358118777, createdTime=Wed Jan 12 03:02:26 CST 2022, time=2022-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712848, encodeId=146b1e12848cd, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, 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style='color:#2F92EE;'>#IGRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9529, encryptionId=a641952930, topicName=IGRA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6cc1239, createdName=sodoo, createdTime=Sun Feb 13 07:02:26 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1921836, encodeId=49cc19218368f, content=<a href='/topic/show?id=4f0a6469837' target=_blank style='color:#2F92EE;'>#治疗药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64698, encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Aug 15 03:02:26 CST 2021, time=2021-08-15, status=1, ipAttribution=), 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createdBy=d39f177, createdName=lixiao3326, createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386783, encodeId=1f031386e83ed, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559069, encodeId=005b1559069b7, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565078, encodeId=150e15650e8f8, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Thu Jul 01 15:02:26 CST 2021, time=2021-07-01, status=1, ipAttribution=)]
    2021-11-17 DEXTER3139
  7. [GetPortalCommentsPageByObjectIdResponse(id=1813688, encodeId=0ed1181368879, content=<a href='/topic/show?id=5f3493451ce' target=_blank style='color:#2F92EE;'>#转移治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93451, encryptionId=5f3493451ce, topicName=转移治疗)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/xkicoVBAnV4HxvdCqC1viaW8wdLQdN9hVP9icgqqDsxC6UVPjfhogdfc2iaU1xNUMVlFl5QicicWrjWQBTsVye5ngOQQ/132, createdBy=f92f2500185, createdName=ms7405317358118777, createdTime=Wed Jan 12 03:02:26 CST 2022, time=2022-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712848, encodeId=146b1e12848cd, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, 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  8. 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  9. 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  10. 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溶瘤病毒诱导自体免疫细胞攻击转移性黑色素瘤,有效治疗了近40%无法进行手术切除的肿瘤患者。

EJC:转移性黑色素瘤患者中血浆总游离DNA作为肿瘤负担和预后评价的替代性标志物

一般来说,在肿瘤患者的血液中, cfDNA水平较高。而且高水平的cfDNA与患者的不良预后有关。然而,肿瘤负担难以测量,并且目前没有可靠的替代生物标记物来可靠地进行评价和确定。本研究的目的是评估血浆总细胞游离DNA作为肿瘤负荷和转移性黑素瘤患者预后的生物标志物的潜力。 研究人员开展了一项关于生物标志物的前瞻性队列研究。在43名转移性黑素瘤患者中进行了总血浆循环无细胞DNA(cfDNA)浓度

NEJM:Dabrafenib加Trametinib治疗转移性黑色素瘤的五年疗效

由此可见,大约三分之一的携带有BRAF V600E或V600K突变的不可切除或转移性黑色素瘤患者可从dabrafenib加trametinib的一线治疗中获得长期益处。

JAMA Dermatology:抗PD-1疗法可降低伊匹单抗相关免疫副反应风险

自2011年以来,许多转移性黑色素瘤患者接受了伊匹单抗(ipilimumab)单药治疗,但随即出现了严重的免疫相关不良事件。

Br J Cancer:免疫检查点阻断治疗诱导的自身免疫与转移性黑色素瘤的预后和独特的T细胞表达谱相关

免疫检查点阻断(ICB)疗法是一类通过介导T细胞活性来提高抗肿瘤免疫反应的治疗方法。

Cell Death Differ:Fra-2/AP-1下调Fam212b表达调节黑色素瘤细胞的转移

目前转移性黑色素瘤仍是具有挑战性的疾病之一,患者的临床结局较差。尽管有一部分转移性黑素瘤患者受益于新疗法,但转移的发生也与患者的不良预后息息相关。转移是一个多步骤过程,涉及癌细胞在远端器官的分离、迁移