Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration
Abstract
:1. Introduction
2. Mechanisms of Resistance to CDK4/6 Inhibitors
2.1. Cell Cycle Mediators as Resistance Biomarkers
2.2. Oncogenic Signaling Pathways Promoting CDK4/6 Inhibitor Resistance
2.3. The Role of DNA Damage Response and Repair Deficiency in the Promotion of CDK4/6 Inhibitor Resistance
2.4. The Role of the Microenvironment in the CDK4/6 Inhibitor Response
3. The Use of Liquid Biopsy for Biomarker Identification
3.1. Circulating Tumor DNA
3.2. Circulating Free RNA
4. MiRNAs as a Tool for Response Prediction to CDK4/6 Inhibitors
4.1. miRNAs Promoting CDK 4/6 Inhibitors Sensitivity
4.2. miRNAs Promoting CDK 4/6 Inhibitor Resistance
5. CDK4/6 Inhibitors in TNBC and Additional Hints on Resistance Mechanisms
6. Additional Cancer Genomic Alterations Involved in Resistance to CDK4/6 Inhibitors
7. Discussion
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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miRNA | Tumor | CDK4/6I | Deregulation | Effect | Reference |
---|---|---|---|---|---|
CDK4/6I SENSITIVITY | |||||
miR-326 | HER2+ BC | Ribociclib | Upregulation | Increased ribociclib sensitivity (antiproliferation activity on BC cells) | [56] |
miR-29b-3p | Luminal, HER2+ BC | Palbociclib | Upregulation (c-myc) | Sensitization to palbociclib (reduces epithelial–mesenchymal transition) | [57] |
miR-126 | Lumina, HER2+ BC | Ribociclib | Upregulation | Sensitization to palbociclib (targets cell cycle genes) | [56] |
miR-3613-3p | TNBC | Palbociclib | Upregulation | Sensitization to palbociclib (regulates SMAD2 and EZH2 expression) | [58] |
CDK4/6I resistance | |||||
miR-432-5p | ER+ BC | Palbociclib Ribociclib | Upregulation | Resistance to palbociclib (suppresses SMAD4 and TGF-β pathway) | [59] |
miR-223 | Luminal, HER2+ BC | Palbociclib | Downregulation | Resistance to palbociclib (associated with activation of E2F1) | [60] |
miR-106b | ER+ BC | Palbociclib | Downregulation | Resistance to palbociclib (modulation of MCM7 RB/E2F expression) | [61] |
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Krasniqi, E.; Goeman, F.; Pulito, C.; Palcau, A.C.; Ciuffreda, L.; Di Lisa, F.S.; Filomeno, L.; Barba, M.; Pizzuti, L.; Cappuzzo, F.; et al. Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration. Int. J. Mol. Sci. 2022, 23, 14534. https://doi.org/10.3390/ijms232314534
Krasniqi E, Goeman F, Pulito C, Palcau AC, Ciuffreda L, Di Lisa FS, Filomeno L, Barba M, Pizzuti L, Cappuzzo F, et al. Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration. International Journal of Molecular Sciences. 2022; 23(23):14534. https://doi.org/10.3390/ijms232314534
Chicago/Turabian StyleKrasniqi, Eriseld, Frauke Goeman, Claudio Pulito, Alina Catalina Palcau, Ludovica Ciuffreda, Francesca Sofia Di Lisa, Lorena Filomeno, Maddalena Barba, Laura Pizzuti, Federico Cappuzzo, and et al. 2022. "Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration" International Journal of Molecular Sciences 23, no. 23: 14534. https://doi.org/10.3390/ijms232314534