Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma

被引:10
|
作者
Julve, Maximilian [1 ]
Clark, James J. [1 ]
Lythgoe, Mark P. [1 ]
机构
[1] Imperial Coll London, Dept Surg & Canc, London, England
关键词
Melanoma; cyclin-dependent kinases inhibitors; CDK inhibitors; palbociclib; ribociclib; abemaciclib; CELL-CYCLE; RETINOBLASTOMA PROTEIN; PHASE-I; CDK4/6; INHIBITION; RIBOCICLIB LEE011; DOSE-ESCALATION; GROWTH-FACTOR; FLAVOPIRIDOL; CANCER; TRANSCRIPTION;
D O I
10.1080/14656566.2020.1828348
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin-dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen.
引用
收藏
页码:351 / 361
页数:11
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