Treating cancer with selective CDK4/6 inhibitors

被引：0
|
作者：
Ben O'Leary
Richard S. Finn
Nicholas C. Turner
机构：
[1] The Breakthrough Breast Cancer Research Centre,Division of Haematology/Oncology
[2] The Institute of Cancer Research,undefined
[3] Geffen School of Medicine at UCLA,undefined
[4] Breast Unit,undefined
[5] Royal Marsden Hospital,undefined
来源：
Nature Reviews Clinical Oncology | 2016年 / 13卷
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摘要：
The actions of cyclin-dependent kinases (CDK) 4/6, through phosphorylation of retinoblastoma-associated protein 1 (RB1) are pivotal in the transition from G1 to S phase in many cancer cellsThe effectiveness of non-selective inhibition of CDKs is hampered by toxicities, selective CDK4/6 inhibition results in fewer toxicities and also provides promising antitumour effectiveness in various tumour typesEvidence of antitumour activity from phase III trials is currently available for palbociclib in patients with hormone-receptor (HR) positive metastatic breast cancer that have progressed on prior endocrine therapyCDK4/6 inhibitors are most effective in combination with endocrine therapy in patients with HR-positive breast cancer: preclinical data support the combination of CDK4/6 inhibitors with PI3K and/or MAPK inhibitorsLoss of RB1 function is an established mechanism of primary resistance to CDK4/6 inhibitors in vitro, but this, and other biomarkers are yet to be validated clinically
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页码：417 / 430
页数：13
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