文章：

细胞周期蛋白依赖性激酶（CDK）4/6在卵巢组织中的作用及其外源性抑制的可能影响

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

原文发布日期：10 October 2023

DOI: 10.3390/cancers15204923

类型: Article

开放获取: 是

英文摘要：

The combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy is the standard treatment for patients with HR+/HER2− advanced breast cancer. Recently, this combination has also entered the early setting as an adjuvant treatment in patients with HR+/HER2− disease at a high risk of disease recurrence following (neo)adjuvant chemotherapy. Despite their current use in clinical practice, limited data on the potential gonadotoxicity of CDK4/6 inhibitors are available. Hence, fully informed treatment decision making by premenopausal patients concerned about the potential development of premature ovarian insufficiency and infertility with the proposed therapy remains difficult. The cell cycle progression of granulosa and cumulus cells is a critical process for ovarian function, especially for ensuring proper follicular growth and acquiring competence. Due to the pharmacological properties of CDK4/6 inhibitors, there could be a potentially negative impact on ovarian function and fertility in women of reproductive age. This review aims to summarize the role of the cyclin D-CDK4 and CDK6 complexes in the ovary and the potential impact of CDK4/6 inhibition on its physiological processes.

摘要翻译： 

细胞周期蛋白依赖性激酶（CDK）4/6抑制剂联合内分泌治疗是HR+/HER2−晚期乳腺癌患者的标准治疗方案。近期，该联合方案亦作为辅助治疗手段进入早期治疗领域，适用于接受（新）辅助化疗后具有高复发风险的HR+/HER2−乳腺癌患者。尽管CDK4/6抑制剂已在临床实践中应用，但关于其潜在性腺毒性的数据仍十分有限。因此，对于关注治疗可能引发卵巢功能早衰及不孕风险的绝经前患者而言，要做出充分知情的治疗决策仍面临困难。颗粒细胞与卵丘细胞的细胞周期进程是卵巢功能的关键环节，尤其对确保卵泡正常生长及获得发育潜能至关重要。基于CDK4/6抑制剂的药理学特性，可能对育龄期女性的卵巢功能及生育能力产生潜在负面影响。本综述旨在系统阐述细胞周期蛋白D-CDK4/6复合体在卵巢中的作用机制，并探讨CDK4/6抑制对其生理过程的潜在影响。

原文链接：

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition