OBJECTIVE: This review emphasizes the role of cyclin-dependent kinases (CDKs) in neutrophil activation and inflammation. It aims to highlight the therapeutic potential of repurposing CDK inhibitors to manage neutrophilic inflammation, particularly in ARDS and psoriasis. Additionally, it discusses the necessary precautions for the clinical application of these inhibitors due to potential off-target effects and the need for dose optimization.
UNASSIGNED: CDKs regulate key neutrophilic functions, including chemotactic responses, degranulation, NET formation, and apoptosis. Repurposing CDK inhibitors, originally developed for cancer treatment, shows promise in controlling neutrophilic inflammation. Clinical anticancer drugs, palbociclib and ribociclib, have demonstrated efficacy in treating neutrophilic ARDS and psoriasis by targeting off-label pathways, phosphoinositide 3-kinase (PI3K) and phosphodiesterase 4 (PDE4), respectively. While CDK inhibitors offer promising therapeutic benefits, their clinical repurposing requires careful consideration of off-target effects and dose optimization. Further exploration and clinical trials are necessary to ensure their safety and efficacy in treating inflammatory conditions.
目的:这篇综述强调了细胞周期蛋白依赖性激酶(CDKs)在中性粒细胞活化和炎症中的作用。它旨在强调重新利用CDK抑制剂来管理中性粒细胞炎症的治疗潜力,特别是ARDS和牛皮癣。此外,它讨论了由于潜在的脱靶效应和剂量优化的需要,这些抑制剂的临床应用的必要预防措施。
■CDK调节关键的嗜中性粒细胞功能,包括趋化反应,脱粒,NET形成,和凋亡。再利用CDK抑制剂,最初是为癌症治疗而开发的,显示出控制中性粒细胞炎症的希望。临床抗癌药物,palbociclib和ribociclib,已证明通过靶向标记外途径治疗中性粒细胞性ARDS和牛皮癣的功效,磷酸肌醇3-激酶(PI3K)和磷酸二酯酶4(PDE4),分别。虽然CDK抑制剂提供有希望的治疗益处,他们的临床再利用需要仔细考虑脱靶效应和剂量优化.需要进一步的探索和临床试验,以确保其在治疗炎症中的安全性和有效性。