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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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977624001942 |
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| author | L. Foffano L. Cucciniello E. Nicolò I. Migliaccio C. Noto C. Reduzzi L. Malorni M. Cristofanilli L. Gerratana F. Puglisi |
| author_facet | L. Foffano L. Cucciniello E. Nicolò I. Migliaccio C. Noto C. Reduzzi L. Malorni M. Cristofanilli L. Gerratana F. Puglisi |
| author_sort | L. Foffano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-490f7073d3b34cd6970033c59d363c22 |
| institution | Kabale University |
| issn | 1532-3080 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj-art-490f7073d3b34cd6970033c59d363c222025-02-12T05:30:36ZengElsevierBreast1532-30802025-02-0179103863Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find themL. Foffano0L. Cucciniello1E. Nicolò2I. Migliaccio3C. Noto4C. Reduzzi5L. Malorni6M. Cristofanilli7L. Gerratana8F. Puglisi9Department of Medical Oncology. CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, ItalyDepartment of Medical Oncology. CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, ItalyDivision of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy''Sandro Pitigliani'' Translational Research Unit, Hospital of Prato, 59100, Prato, ItalyDepartment of Medical Oncology. CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, ItalyDivision of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA''Sandro Pitigliani'' Translational Research Unit, Hospital of Prato, 59100, Prato, Italy; ''Sandro Pitigliani'' Medical Oncology Department, Hospital of Prato, 59100, Prato, ItalyDivision of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USADepartment of Medical Oncology. CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Corresponding author.Department of Medical Oncology. CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, ItalyCDK4/6 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.http://www.sciencedirect.com/science/article/pii/S0960977624001942Metastatic breast cancerCDK 4/6 inhibitors resistanceLiquid biopsy |
| spellingShingle | L. Foffano L. Cucciniello E. Nicolò I. Migliaccio C. Noto C. Reduzzi L. Malorni M. Cristofanilli L. Gerratana F. Puglisi Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them Breast Metastatic breast cancer CDK 4/6 inhibitors resistance Liquid biopsy |
| title | Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them |
| title_full | Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them |
| title_fullStr | Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them |
| title_full_unstemmed | Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them |
| title_short | Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them |
| title_sort | cyclin dependent kinase 4 and 6 inhibitors cdk4 6i mechanisms of resistance and where to find them |
| topic | Metastatic breast cancer CDK 4/6 inhibitors resistance Liquid biopsy |
| url | http://www.sciencedirect.com/science/article/pii/S0960977624001942 |
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