Department of Hematology Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Hematology Oncology, Taussig Cancer Institute; Lerner College of Medicine, Cleveland Clinic, Cleveland.
Expert Opin Drug Discov. 2021 May;16(5):485-496. doi: 10.1080/17460441.2021.1853097. Epub 2021 Jan 12.
: Cyclin-dependent kinase (CDK) 4/6 inhibitors have altered the standard-of-care treatment for patients with ER-positive, HER2-negative metastatic breast cancer. One such inhibitor, abemaciclib, a reversible ATP-competitive CDK4/6 inhibitor developed by Eli Lilly and Company, was approved by the FDA for ER-positive, HER2-negative metastatic breast cancer.: Preclinical studies revealed abemaciclib's distinct structure, efficacy as monotherapy, and ability to penetrate the Central Nervous System. In this review, the authors have examined the literature regarding the development of CDK 4/6 inhibitors before providing a focused review on the preclinical discovery and development of abemaciclib. The authors then conclude their manuscript by providing their expert opinion and future perspectives.: Understanding the genesis and evolution from concept to approval and beyond will allow one to analyze the impact of abemaciclib. With its unique characteristics, abemaciclib has provided a meaningful addition to the therapeutic arsenal for metastatic breast cancer. There is, however, a need for predictive biomarkers to identify patients who may not benefit from or may develop resistance to CDK4/6 inhibition.
细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂改变了 ER 阳性、HER2 阴性转移性乳腺癌患者的标准治疗方法。其中一种抑制剂 abemaciclib 是由礼来公司开发的一种可逆的 ATP 竞争性 CDK4/6 抑制剂，已获得 FDA 批准用于治疗 ER 阳性、HER2 阴性转移性乳腺癌。临床前研究揭示了 abemaciclib 的独特结构、单药疗效以及穿透中枢神经系统的能力。在这篇综述中，作者首先检查了关于 CDK 4/6 抑制剂的发展的文献，然后提供了对 abemaciclib 的临床前发现和开发的重点回顾。最后，作者通过提供他们的专家意见和未来展望来结束他们的手稿。了解从概念到批准及以后的起源和演变，将有助于分析 abemaciclib 的影响。由于其独特的特性，abemaciclib 为转移性乳腺癌的治疗武器库增添了有意义的新选择。但是，需要有预测性生物标志物来识别可能无法从 CDK4/6 抑制中获益或可能产生耐药性的患者。
