细胞周期蛋白依赖激酶
细胞周期蛋白依赖激酶6
癌症研究
细胞生长
细胞周期
激酶
E2F型
视网膜母细胞瘤蛋白
帕博西利布
转录因子
生物
视网膜母细胞瘤
信号转导
过渡(遗传学)
癌细胞
癌症
细胞生物学
癌症治疗
细胞
化学
细胞周期蛋白
细胞周期进展
靶向治疗
计算生物学
小分子
限制点
细胞周期蛋白D1
生物信息学
PI3K/AKT/mTOR通路
作者
Seth M. Rubin,Julien Sage,Jan M. Skotheim
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2026-01-05
卷期号:86 (7): 1545-1557
被引量:1
标识
DOI:10.1158/0008-5472.can-25-0916
摘要
At its core, cancer is a disease of uncontrolled cell proliferation mediated by perturbed molecular pathways that have been elucidated over the past few decades. Biochemical and genetic studies have identified the key molecular regulators of the transition from G1 to S phase in the cell cycle that commits cells to division. During the G1/S transition, the cyclin-dependent kinases CDK4 and CDK6 (CDK4/6) form complexes with cyclin D that phosphorylate and inhibit the retinoblastoma protein. The resulting activation of E2F transcription factors then drives progression into S phase. The centrality of the G1/S transition for proliferation motivated the development of small-molecule ATP-competitive CDK4/6 inhibitors, which block the first step of this pathway and are now standard of care for some forms of breast cancer. Although successful, these therapeutics have limitations that have motivated the development of alternative approaches to targeting CDKs and the cell cycle. Here, we review how recently developed inhibitors of CDKs and other components of the G1/S pathway may be used, as single agents or in combination therapies, to oppose the growth of human cancers.
科研通智能强力驱动
Strongly Powered by AbleSci AI