文章：

乳腺癌中CDK4/6抑制剂疗效与耐药性的演变通路

The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer

原文发布日期：2 October 2023

DOI: 10.3390/cancers15194835

类型: Article

开放获取: 是

英文摘要：

The approval of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has remarkably improved the survival outcomes of patients with advanced hormone receptor-positive (HR+) breast cancer (BC), becoming the new standard of care treatment in these patients. Despite the efficacy of this therapeutic combination, intrinsic and acquired resistance inevitably occurs and represents a major clinical challenge. Several mechanisms associated with resistance to CDK4/6i have been identified, including both cell cycle-related and cell cycle-nonspecific mechanisms. This review discusses new insights underlying the mechanisms of action of CDK4/6i, which are more far-reaching than initially thought, and the currently available evidence of the mechanisms of resistance to CDK4/6i in BC. Finally, it highlights possible treatment strategies to improve CDK4/6i efficacy, summarizing the most relevant clinical data on novel combination therapies involving CDK4/6i.

摘要翻译： 

细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）联合内分泌治疗（ET）的获批显著改善了晚期激素受体阳性（HR+）乳腺癌（BC）患者的生存结局，已成为这类患者的新标准治疗方案。尽管该联合疗法疗效显著，但内在性与获得性耐药问题仍不可避免，成为当前临床面临的主要挑战。目前已发现多种与CDK4/6i耐药相关的机制，包括细胞周期相关及非特异性机制。本文综述了CDK4/6i作用机制的新认知（其影响远比最初设想的更为深远），并系统梳理了目前关于乳腺癌CDK4/6i耐药机制的现有证据。最后，通过总结涉及CDK4/6i新型联合疗法的最具相关性临床数据，重点探讨了提升CDK4/6i疗效的潜在治疗策略。

原文链接：

The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer