Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6iss) are widely used in first-line metastatic breast cancer. For patients with progression under CDK4/6is, there is currently no standard treatment recommended at the category 1 level in international guidelines. The purpose of this article is to review...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-09, Vol.24 (19), p.14427
Main Authors: Villa, Federica, Crippa, Alessandra, Pelizzoni, Davide, Ardizzoia, Alessandra, Scartabellati, Giulia, Corbetta, Cristina, Cipriani, Eleonora, Lavitrano, Marialuisa, Ardizzoia, Antonio
Format: Article
Language:English
Subjects:
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cancer therapies
CDK 4/6 inhibitors
Cell Cycle
Cell division
cell-cycle-specific and non-specific resistance
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Cyclin-dependent kinases
Female
Growth factors
Humans
Kinases
Metastasis
metastatic breast cancer
Mutation
Phosphorylation
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Proteins
Review
Transcription factors
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Summary:Cyclin-dependent kinase 4/6 inhibitors (CDK4/6iss) are widely used in first-line metastatic breast cancer. For patients with progression under CDK4/6is, there is currently no standard treatment recommended at the category 1 level in international guidelines. The purpose of this article is to review the cellular mechanisms underlying the resistance to CDK4/6is, as well as treatment strategies and the clinical data about the efficacy of subsequent treatments after CDK4/6is-based therapy. In the first part, this review mainly discusses cell-cycle-specific and cell-cycle-non-specific resistance to CDK4/6is, with a focus on early and late progression. In the second part, this review analyzes potential therapeutic approaches and the available clinical data on them: switching to other CDK4/6is, to another single hormonal therapy, to other target therapies (PI3K, mTOR and AKT) and to chemotherapy.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241914427