Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews Pub Date : 2025-06-14 DOI:10.1016/j.ctrv.2025.102980

Federica Giugliano , Carmine De Angelis , Barbara Pistilli , Giulia Viale , Giampaolo Bianchini , Mario Giuliano , Luca Malorni , Beatrice Taurelli Salimbeni , Angela Esposito , Antonio Giordano , Timothy A. Yap , Giuseppe Curigliano , Carmen Criscitiello

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引用次数: 0

Abstract

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations. In this review, we discuss the mechanisms of action and resistance to CDK4/6i, providing a comprehensive overview of emerging efficacy and safety data, biomarker-driven strategies, and ongoing clinical trials. Finally, we delineate key research priorities aimed at guiding the development of innovative therapeutic combinations.

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在激素受体阳性，HER2阴性乳腺癌中克服对CDK4/6抑制剂的耐药性：创新组合和新兴策略

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）可改善转移性和早期激素受体阳性、her2阴性乳腺癌患者的预后。然而，大约20%的这些肿瘤对这些治疗表现出内在的耐药性，并且大多数发展为获得性耐药机制，从而推动进展。对接受CDK4/6i + ET治疗的患者的生物样本进行生物标志物分析，已经确定了治疗组合的潜在靶点。在这篇综述中，我们讨论了CDK4/6i的作用机制和耐药性，提供了新出现的疗效和安全性数据、生物标志物驱动策略和正在进行的临床试验的全面概述。最后，我们描述了关键的研究重点，旨在指导创新治疗组合的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer treatment reviews 医学-肿瘤学

CiteScore

21.40

自引率

0.80%

发文量

109

审稿时长

13 days

期刊介绍： Cancer Treatment Reviews Journal Overview: International journal focused on developments in cancer treatment research Publishes state-of-the-art, authoritative reviews to keep clinicians and researchers informed Regular Sections in Each Issue: Comments on Controversy Tumor Reviews Anti-tumor Treatments New Drugs Complications of Treatment General and Supportive Care Laboratory/Clinic Interface Submission and Editorial System: Online submission and editorial system for Cancer Treatment Reviews