Abstract：
Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6is) in combination with Endocrine Therapy (ET) represent the standard frontline therapy for patients with Hormone Receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic Breast Cancer (mBC). Clinical activity and efficacy of CDK4/6is-based therapies have been proven both in the endocrine sensitive and resistant settings. Therapy resistance eventually underpins clinical progression to any CDK4/6is-based therapies, yet there is a lack of validated molecular biomarkers predictive of either intrinsic or acquired resistance to CDK4/6is in clinical practice. As the \"post-CDK4/6is\" landscape for the management of HR-positive/HER2-negative mBC is rapidly evolving with the introduction of novel therapies, there is an urgent need for the definition of clinically relevant molecular biomarkers of intrinsic/acquired resistance mechanisms to CDK4/6is. This narrative review outlines the role of currently approved CDK4/6is-based therapies, describes the most relevant molecular biomarkers of CDK4/6is-resistance, and ultimately provides a perspective on the clinical and research scenario.
摘要：
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6is）与内分泌治疗（ET）联合代表激素受体（HR）阳性患者的标准一线治疗，人表皮生长因子受体2（HER2）阴性转移性乳腺癌（mBC）。基于CDK4/6is的疗法的临床活性和功效已在内分泌敏感和耐药环境中得到证实。治疗抵抗最终支持任何基于CDK4/6IS的治疗的临床进展，然而,在临床实践中,缺乏可预测CDK4/6is固有或获得性耐药的有效的分子生物标志物.随着新疗法的引入，HR阳性/HER2阴性mBC的“CDK4/6is”管理景观正在迅速发展，迫切需要定义CDK4/6is固有/获得性耐药机制的临床相关分子生物标志物.这篇叙述性综述概述了目前批准的基于CDK4/6IS的疗法的作用。描述了CDK4/6is抗性的最相关的分子生物标志物，并最终提供了对临床和研究情景的看法。
