通过功能基因组学解析乳腺癌内分泌耐药的复杂性。

Unraveling the complexity of endocrine resistance in breast cancer by functional genomics.

作者信息

Swanton Charles, Downward Julian

机构信息

Cancer Research UK London Research Institute, Signal Transduction Laboratory, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

出版信息

Cancer Cell. 2008 Feb;13(2):83-5. doi: 10.1016/j.ccr.2008.01.021.

DOI:10.1016/j.ccr.2008.01.021

PMID:18242507

Abstract

Despite the proven benefit of antiestrogen drugs in breast cancer treatment, resistant disease ultimately develops in advanced breast cancer. In this issue of Cancer Cell, Iorns et al. find that loss of CDK10 expression promotes resistance of cells to tamoxifen and is associated with poor outcome in breast cancer patients treated with the drug. CDK10 loss increases the activity of the transcription factor ETS2 on the promoter of the RAF1 gene, elevating ERK/MAPK kinase pathway activity and relieving tamoxifen-induced G1 arrest. CDK10 is thus a potential biomarker for sensitivity in prospective clinical trials of patients treated with endocrine therapies.

摘要

尽管抗雌激素药物在乳腺癌治疗中的益处已得到证实，但晚期乳腺癌最终仍会出现耐药性疾病。在本期《癌细胞》杂志中，约恩斯等人发现，细胞周期蛋白依赖性激酶10（CDK10）表达缺失会促进细胞对他莫昔芬的耐药性，并且与接受该药物治疗的乳腺癌患者的不良预后相关。CDK10缺失会增加转录因子ETS2对RAF1基因启动子的活性，提高细胞外信号调节激酶/丝裂原活化蛋白激酶（ERK/MAPK）信号通路的活性，并解除他莫昔芬诱导的G1期阻滞。因此，在接受内分泌治疗患者的前瞻性临床试验中，CDK10是敏感性的潜在生物标志物。