Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the antitumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate potent cooperation between CDK4/6i and chemotherapy. Furthermore, the combination of CDK4/6i and chemotherapy is being tested in clinical trials to both enhance antitumor efficacy and limit toxicity. Exploitation of the noncanonical effects of CDK4/6i could also provide an impetus for future studies in combination with chemotherapy. Thus, while seemingly mutually exclusive mechanisms are at play, the combination of CDK4/6 inhibition and chemotherapy could exemplify rational medicine.

中文翻译：

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化疗和 CDK4/6 抑制剂：意想不到的同床异梦

细胞周期蛋白依赖性激酶 4 和 6 (CDK4/6) 已成为重要的治疗靶点。这些激酶的药理学抑制剂可抑制细胞周期进程并对肿瘤和宿主环境产生其他重要影响。由于它们对细胞周期的影响，CDK4/6 抑制剂 (CDK4/6i) 被假设可以拮抗细胞毒性化疗对 CDK4/6 依赖性肿瘤的抗肿瘤作用。然而，多项临床前研究表明 CDK4/6i 与化疗之间具有有效的协同作用。此外，CDK4/6i 和化疗的组合正在临床试验中进行测试，以增强抗肿瘤功效并限制毒性。利用 CDK4/6i 的非典型效应也可以为未来与化疗联合的研究提供动力。因此，虽然看似相互排斥的机制在发挥作用，但 CDK4/6 抑制和化疗的结合可以成为合理医学的例证。