CDK4/6 Inhibition in Breast Cancer: Mechanisms of Response and Treatment Failure.
CDK4/6 Inhibition in Breast Cancer: Mechanisms of Response and Treatment Failure.
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DOI：
10.1007/s12609-017-0232-0
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发表时间：
2017-03
影响因子：
0.9
通讯作者：
Goel S
中科院分区：
文献类型：
--
作者：
Garrido-Castro AC;Goel S
描述d型细胞周期蛋白和cdk4和cdk6在乳腺癌中的作用，并讨论对CDK4/6抑制剂敏感或耐药的潜在生物标志物。少量临床前和临床研究已经探索了CDK4/6抑制剂在乳腺癌中的反应和耐药的潜在机制。推测的应答标志包括er阳性、腔内基因表达模式、高cyclin D1水平和低p16水平。可能的耐药机制包括Rb功能丧失、细胞周期蛋白E过表达/扩增和CDK6扩增。其中大多数仍然是推测性的，尚未在临床标本中得到验证。如果要利用CDK4/6抑制剂的早期成功，我们对乳腺癌中CDK4/6生物学的理解要超越目前的初级状态，这一点至关重要。只有这样，我们才能开发出合理的治疗组合，进一步提高这些药物的疗效。
To describe the role of D-type cyclins and CDKs 4 and 6 in breast cancer, and to discuss potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors. A small number of preclinical and clinical studies have explored potential mechanisms of CDK4/6 inhibitor response and resistance in breast cancer. Putative markers of response include ER-positivity, luminal patterns of gene expression, high cyclin D1 levels, and low p16 levels. Possible resistance mechanisms include loss of Rb function, overexpression/amplification of cyclin E, and CDK6 amplification. Most these remain speculative and have not been validated in clinical specimens. If early successes with CDK4/6 inhibitors are to be capitalized upon, it is critical that our understanding of CDK4/6 biology in breast cancer extends beyond its current rudimentary state. Only then we will be able to develop rational therapeutic combinations that further enhance the efficacy of these agents.