帕博西利布
背景(考古学)
重新调整用途
药物重新定位
临床试验
细胞周期蛋白依赖激酶
药理学
激酶
自噬
癌症
药物发现
生物
医学
药品
细胞周期
乳腺癌
生物信息学
转移性乳腺癌
内科学
细胞凋亡
细胞生物学
古生物学
生物化学
生态学
作者
Denisa Hendrychová,Radek Jorda,Vladimı́r Kryštof
摘要
Pharmacological inhibition of cyclin-dependent kinase 4/6 (CDK4/6) has emerged as an efficient approach for treating breast cancer, and its clinical potential is expanding to other cancers. CDK4/6 inhibitors were originally believed to act by arresting proliferation in the G1 phase, but it is gradually becoming clear that the cellular response to these compounds is far more complex than this. Multiple context-dependent mechanisms of action are emerging, involving modulation of quiescence, senescence, autophagy, cellular metabolism, and enhanced tumor cell immunogenicity. These mechanisms may be driven by interactions with unexpected targets. We review cellular responses to the Food and Drug Administration-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib, and summarize available knowledge of other drugs undergoing clinical trials, including data on their off-target landscapes. We emphasize the importance of comprehensively characterizing drugs' selectivity profiles to maximize their clinical efficacy and safety and to facilitate their repurposing to treat additional diseases based on their target spectrum.
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