Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been a...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-09, Vol.21 (18), p.6479
Main Authors: Piezzo, Michela, Cocco, Stefania, Caputo, Roberta, Cianniello, Daniela, Gioia, Germira Di, Lauro, Vincenzo Di, Fusco, Giuseppina, Martinelli, Claudia, Nuzzo, Francesco, Pensabene, Matilde, De Laurentiis, Michelino
Format: Article
Language:English
Subjects:
Biomarkers, Pharmacological - analysis
Biomarkers, Pharmacological - metabolism
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer therapies
Cell cycle
Cell Cycle - drug effects
Cell Cycle - physiology
Cell division
Clinical trials
Cyclin D
Cyclin-dependent kinase
Cyclin-dependent kinase 4
Cyclin-Dependent Kinase 4 - antagonists & inhibitors
Cyclin-Dependent Kinase 4 - metabolism
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
Cyclin-Dependent Kinase 6 - metabolism
Cyclin-dependent kinases
Deregulation
Drug delivery
Drug development
Drugs
Endocrine therapy
ErbB-2 protein
Gene amplification
Growth factors
Kinases
Metastases
Metastasis
Phosphorylation
Piperazines - pharmacology
Protein Kinase Inhibitors - pharmacology
Proteins
Purines - pharmacology
Pyridines - pharmacology
Receptor, ErbB-2 - metabolism
Receptors, Estrogen - metabolism
Review
Tumors
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Summary:Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21186479