CLIN CANCER RES:cyclin E过表达使三阴性乳腺癌对Wee1激酶抑制剂敏感

2018-12-23 MedSci MedSci原创

三阴性乳腺癌(TNBC)预后不良是由于其侵袭性较强且缺乏有效的靶向治疗。cyclin E和磷酸化CDK2的过度表达与TNBC患者的不良预后相关,并且CDK2的缺失使细胞对Wee1激酶抑制脱敏。CLIN CANCER RES近期发表了一篇文章,研究cyclin E的表达是否可以预测TNBC对包括Wee1激酶抑制剂AZD1775在内的治疗反应。

三阴性乳腺癌(TNBC)预后不良是由于其侵袭性较强且缺乏有效的靶向治疗。cyclin E和磷酸化CDK2的过度表达与TNBC患者的不良预后相关,并且CDK2的缺失使细胞对Wee1激酶抑制脱敏。CLIN CANCER RES近期发表了一篇文章,研究cyclin E的表达是否可以预测TNBC对包括Wee1激酶抑制剂AZD1775在内的治疗反应。

作者在表达不同cyclin E的TNBC细胞系和异种移植物(PDX)模型中评估AZD1775的单药和联合疗法的效果。通过诱导cyclin E表达或CRISPR / Cas9敲除研究cyclin E发挥作用的机制。研究结果表明,cyclin E过表达使TNBC细胞系和PDX模型对AZD1775敏感,导致DNA复制应激通路的CDK2依赖性激活,增加Wee1激酶活性。此外,用CDK2抑制剂或卡铂处理细胞可以导致cyclin E的转录诱导并导致DNA复制应激。在TNBC细胞和PDX模型中,这种药物介导的cyclin E增加使TNBC对AZD1775敏感。

文章最后认为,cyclin E是治疗反应的潜在生物标志物,包括AZD1775单药治疗cyclin E-高TNBC和CDK2抑制剂或卡铂联合AZD172治疗cyclin E-低TNBC。

原始出处:

Xian Chen, Kwang-Huei Low, et al. Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition. CLIN CANCER RES. December 2018 doi: 10.1158/1078-0432.CCR-18-1446

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    2019-02-22 jklm09
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    2019-07-03 lq1767
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    2018-12-25 kafei

    学习了谢谢

    0

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    2018-12-25 xlysu
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    2018-12-25 redcrab

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