CDK4 and CDK6 kinases: From basic science to cancer therapy

被引:165
|
作者
Fassl, Anne [1 ]
Geng, Yan [1 ]
Sicinski, Piotr [1 ]
机构
[1] Harvard Med Sch, Dana Farber Canc Inst, Blavatnik Inst, Dept Canc Biol,Dept Genet, Boston, MA 02215 USA
关键词
CYCLIN-DEPENDENT KINASES; BREAST-CANCER; CELL-CYCLE; PHARMACOLOGICAL INHIBITION; TRANSCRIPTIONAL REGULATION; ACQUIRED-RESISTANCE; ANTITUMOR-ACTIVITY; ENDOCRINE THERAPY; OVARIAN-CANCER; INDUCED DEATH;
D O I
10.1126/science.abc1495
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) and their activating partners, D-type cyclins, link the extracellular environment with the core cell cycle machinery. Constitutive activation of cyclin D-CDK4/6 represents the driving force of tumorigenesis in several cancer types. Small-molecule inhibitors of CDK4/6 have been used with great success in the treatment of hormone receptor-positive breast cancers and are in clinical trials for many other tumor types. Unexpectedly, recent work indicates that inhibition of CDK4/6 affects a wide range of cellular functions such as tumor cell metabolism and antitumor immunity. We discuss how recent advances in understanding CDK4/6 biology are opening new avenues for the future use of cyclin D-CDK4/6 inhibitors in cancer treatment.
引用
收藏
页码:158 / +
页数:20
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