CLIN CANCER RES：HER2阳性乳腺癌T-DM1获得性耐药与Cyclin B1诱导缺陷

2017-11-28 MedSci MedSci原创

Trastuzumab-emtansine（T-DM1）是晚期HER2阳性乳腺癌的标准治疗药物。但是不可避免的会出现肿瘤耐药。CLIN CANCER RES近期发表了一篇文章，研究T-DM1获得性耐药的机制。

Trastuzumab-emtansine（T-DM1）是晚期HER2阳性乳腺癌的标准治疗药物。但是不可避免的会出现肿瘤耐药。CLIN CANCER RES近期发表了一篇文章，研究T-DM1获得性耐药的机制。

作者使用T-DM1处理HER2阳性乳腺癌细胞（HCC1954，HCC1419，SKBR3和BT474）以诱导耐药亚型。比较亲代和耐药亚型由T-DM1引起的细胞和分子的不同。分析CDK1酶活性和Cyclin B1表达情况。研究Cyclin B1基因改变是上调或下调。在HER2阳性乳腺癌模型中研究T-DM1 对Cyclin B1水平，细胞增殖及凋亡的影响。最终得到了三个不同水平T-DM1耐药的细胞系（HCC1954/TDR，HCC1419/TDR，SKBR3/TDR）。在耐药细胞中HER2仍然扩增。耐药细胞中，与HER2结合的以及细胞内摄入的T-DM1依然存在。在敏感细胞中T-DM1可以诱导Cyclin B1聚集，但是在耐药细胞中无此效果。亲代细胞siRNA敲低Cyclin B1可诱导T-DM1耐药，通过沉默cdc20增加Cyclin B1水平可以部分使耐药细胞再敏感。在18个HER2阳性乳腺癌模型中，T-DM1对增殖及凋亡的影响与Cyclin B1累积水平一致。

文章最后认为，T-DM1导致的Cyclin B1诱导缺陷导致HER2阳性乳腺癌出现获得性耐药。该研究结果支持在T-DM1治疗过程中检测Cyclin B1以作为HER2阳性乳腺癌的药效学预测标志。

原始出处：

MohammadA Sabbaghi,Gabriel Gil-Gomez,et al.Defective Cyclin B1 Induction in Trastuzumab-emtansine(T-DM1) Accquired Resistance in HER2-positive Breast Cancer.CLIN CANCER RES.November 2017 doi:10.1158/1078-0432.CCR-17-0696

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2018-10-30 zhaozhouchifen

#获得性耐药#

31 0
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2018-04-10 pandamao2010

#获得性#

35 0
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2017-11-30 闆锋旦

#HER2阳性#

34 0
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2017-11-28 kalery

好文章学习了

79 0
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2017-11-28 戒馋，懒，贪

谢谢分享学习了

74 0

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