Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI, USA.
Expert Opin Pharmacother. 2020 Jun;21(8):941-952. doi: 10.1080/14656566.2020.1738385. Epub 2020 Mar 12.
Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression in both normal and malignant cells, functioning through complex molecular interactions. Deregulation of CDK-dependent pathways is commonly found in both non-small cell and small cell lung cancer, and these derangements suggest vulnerabilities that can be exploited for clinical benefit.
In this review, the authors present an overview of the biology of CDKs in normal and malignant cells, with a focus on lung cancer, followed by an assessment of preclinical work that has demonstrated the vital role of CDKs in lung cancer development and progression, and the activity of CDK inhibitors in a variety of lung cancer models. Finally, the experience with clinical trials of CDK inhibitors in lung cancer is discussed along with the current status of these agents in cancer therapy.
Despite strong biological rationale and promising preclinical studies, the results of clinical trials of CDK inhibitors in lung cancer have thus far been disappointing. Further clinical development of CDK inhibitors in lung cancer will depend on the identification of predictive biomarkers and the design of combination regimens that take advantage of the unique molecular alterations that drive lung cancer growth and survival.
细胞周期蛋白依赖性激酶（CDKs）是正常和恶性细胞中细胞周期进程的关键调节因子，通过复杂的分子相互作用发挥作用。非小细胞肺癌和小细胞肺癌中都常见 CDK 依赖性途径的失调，这些失调表明存在可用于临床获益的脆弱性。
在这篇综述中，作者介绍了 CDK 在正常和恶性细胞中的生物学概述，重点是肺癌，然后评估了表明 CDK 在肺癌发生和进展中的重要作用以及各种肺癌模型中 CDK 抑制剂活性的临床前研究。最后，讨论了 CDK 抑制剂在肺癌中的临床试验经验以及这些药物在癌症治疗中的现状。
尽管具有强烈的生物学依据和有希望的临床前研究，但迄今为止，CDK 抑制剂在肺癌中的临床试验结果令人失望。CDK 抑制剂在肺癌中的进一步临床开发将取决于预测生物标志物的鉴定和联合方案的设计，这些方案利用驱动肺癌生长和存活的独特分子改变。
