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

• 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
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241914427

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.