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Review
. 2023 Sep 22;24(19):14427.
doi: 10.3390/ijms241914427.

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

Federica Villa  1 , Alessandra Crippa  1 , Davide Pelizzoni  1 , Alessandra Ardizzoia  2 , Giulia Scartabellati  3   4 , Cristina Corbetta  1 , Eleonora Cipriani  1 , Marialuisa Lavitrano  2 , Antonio Ardizzoia  1
Affiliations
Review

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

Federica Villa et al. Int J Mol Sci. .

Abstract

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.

Keywords: CDK 4/6 inhibitors; cell-cycle-specific and non-specific resistance; metastatic breast cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cell-cycle-specific mechanisms that could be associated with CDK4/6is resistance. Sharp arrows (→) indicate stimulation, blunt arrows (┴) indicate inhibition.
Figure 2
Figure 2
Cell-cycle-non-specific mechanisms that could be associated with CDK4/6is resistance. Sharp arrows (→) indicate stimulation, blunt arrows (┴) indicate inhibition.
See this image and copyright information in PMC

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