SCI TRANSL MED:脑转移瘤靶向治疗新突破

2017-05-25 cailingrui MedSci原创

通过小鼠模型和人类肿瘤样本,研究人员发现在于乳腺癌相关的脑损伤中,人表皮生长因子受体(HER3)表达量升高,并且展现出接受靶向治疗的情况下,对肿瘤的存活起到促进作用。抑制HER3表达可以有助于克服治疗抗性。

尽管癌症的靶向治疗给患者带来了极大希望,靶向治疗在脑转移瘤上的效果依然远不及外周肿瘤。过去人们普遍认为这是由于药物难以穿透血脑屏障导致的,最近麻省总医院的Kodack等人研究证明,事情并不像我们想象的那样简单。研究发现至少在乳腺癌中,大脑的微环境本身在转移瘤的治疗抗性中扮演重要角色。 通过小鼠模型和人类肿瘤样本,研究人员发现在于乳腺癌相关的脑损伤中,人表皮生长因子受体(HER3)表达量升高,并且展现出接受靶向治疗的情况下,对肿瘤的存活起到促进作用。抑制HER3表达可以有助于克服治疗抗性。 

研究人员采用乳腺癌临床模型,如实的展现了在这种微环境下,与平时完全不同的临床反应。研究发现,尽管靶向药物会积累在脑损伤部位,脑转移瘤依然可以避开PI3K的抑制作用。与外周肿瘤相比,检测到了脑损伤部位HER3表达量的升高和磷酸化反应。通过阻断HER3,克服了HER2阳性及(或)PIK3CA突变型乳腺癌脑转移对PI3K抑制剂的抗性,肿瘤生长得到显著抑制,小鼠生存率得以提升。研究数据展示了大脑微环境在治疗抗性中的作用机制,研究出可应用于HER2阳性及(或)PIK3CA突变型乳腺癌脑转移的治疗策略。


原始出处:
David P. Kodack, et al. The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation. Sci Transl Med. 24 May 2017:Vol. 9, Issue 391, eaah4682 

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    2018-04-02 bsmagic9140
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    2017-06-14 zxxiang
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    2017-05-25 cqykthl

    发现新的靶点可以阻断脑转移瘤的进展

    0

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乳腺癌是意大利和世界妇女中最常见的癌症之一。然而今天,通过数值模拟,似乎可以设计出更有选择性和有效的药物。一项新的研究详细分析了激活参与雌激素合成的重要药理学靶点的机制,超出了实验方法的极限。这项由意大利癌症研究协会资助的研究表明,不同形状和大小的分子进入蛋白质活性区的路径相同,即合成雌性激素的核心蛋白。该研究发表在《物理化学快报》杂志上。细胞色素P450是在不同激素和药物代谢中起关键作用的酶,特

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