Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them

CDK4/6 inhibitors (CDK4/6i) have significantly impacted on the treatment of HR + HER2 negative (HER2-) metastatic breast cancer (BC) when combined with endocrine therapy. Nonetheless, despite significant research efforts, the mechanisms of de novo and acquired resistance to CDK4/6i have not yet been...

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Bibliographic Details
Main Authors: L. Foffano, L. Cucciniello, E. Nicolò, I. Migliaccio, C. Noto, C. Reduzzi, L. Malorni, M. Cristofanilli, L. Gerratana, F. Puglisi
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Breast
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Online Access:http://www.sciencedirect.com/science/article/pii/S0960977624001942
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Summary:CDK4/6 inhibitors (CDK4/6i) have significantly impacted on the treatment of HR + HER2 negative (HER2-) metastatic breast cancer (BC) when combined with endocrine therapy. Nonetheless, despite significant research efforts, the mechanisms of de novo and acquired resistance to CDK4/6i have not yet been fully elucidated, highlighting the need for a deeper understanding of these process. Additionally, the importance of dissecting CDK4/6i resistance from endocrine resistance for personalized treatment is increasingly recognized.Liquid biopsy has emerged as a minimally invasive tool for identifying circulating biomarkers of resistance through the integration of multiparametric and dynamic assessments that encompass ctDNA, CTCs, exosomes, and epigenetic ctDNA alterations, representing a promising perspective for the clinical characterization of treatment resistance and guiding post-progression strategies to improve patient outcomes.Aim of this review is summarize potential mechanisms of CDK4/6i resistance, along with the advantages of using liquid biopsy to identify resistance biomarkers in HR+/HER2- MBC patients treated with CDK 4/6 inhibitors.
ISSN:1532-3080