Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Int J Mol Sci. 2023 Jul 22;24(14):11791. doi: 10.3390/ijms241411791.
The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and the improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor-positive metastatic breast cancer.
CDK4/6 抑制剂（如 palbociclib、ribociclib 和 abemaciclib）的出现彻底改变了激素受体阳性乳腺癌的治疗格局。这些药物在无进展生存期和总生存期方面均显示出显著的临床获益。然而，对 CDK4/6 抑制剂的耐药性仍然是一个挑战，限制了它们的长期疗效。了解导致耐药性的复杂机制对于开发新的治疗策略和改善患者结局至关重要。转化研究（如临床前模型和生物标志物研究）为耐药机制提供了有价值的见解，并可能指导新的联合治疗方法的确定。本综述旨在概述 CDK4/6 抑制剂耐药的报告机制，从临床数据和转化研究中汲取见解，以帮助指导激素受体阳性转移性乳腺癌的未来治疗方向。
