153135 20251017144642.0 doi 10.3390/cancers17050760 sideral 143563 ART-2025-143563 eng Santander Ballestín, Sonia Universidad de Zaragoza (orcid)0000-0002-1275-2600 Advances in CDK4 and 6 inhibitors: transforming breast cancer treatment 2025 Access copy available to the general public Unrestricted Background and Objectives: Breast cancer is the most common malignant neoplasm worldwide and the most prevalent one among women. It represents the leading cause of cancer-related death among females. Cyclin-dependent kinase 4 and 6 inhibitors disrupt the cell cycle, inducing cellular senescence and, ultimately, apoptosis. Consequently, they have become a novel type of adjuvant therapy for the treatment of advanced or metastatic breast cancer characterised by positive hormone receptors and human epidermal growth factor receptor 2 (HER-2) negative. Methods: A systematic review was conducted, analysing the available literature on cyclin-dependent kinase 4 and 6 inhibitors published over the last five years. The aim was to evaluate the efficacy and safety of adding these drugs to the standard endocrine therapy for this pathology. Results: The combination of cyclin-dependent kinase 4 and 6 inhibitors with endocrine therapy was shown to improve progression-free survival, overall survival, and chemotherapy-free intervals in patients who received this combination therapy. Conclusions: The addition of CDK4/6 inhibitors to endocrine therapy in the treatment of advanced or metastatic breast cancer with positive hormone receptors and HER-2 negative significantly improved PFS, median survival, and chemotherapy-free intervals compared with the use of hormonal treatments alone or in combination with a placebo. Currently, CDK4/6 inhibitors are becoming established as a new standard treatment for this pathology, offering lower toxicity than chemotherapy. However, it is necessary to deeply investigate the mechanisms of treatment resistance and develop effective therapies to overcome them. info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Abadía Labena, María Avedillo-Salas, Ana Universidad de Zaragoza (orcid)0000-0003-2153-0417 Marco Continente, Cristina Arribas Blázquez, Marina Luesma Bartolomé, María José Universidad de Zaragoza (orcid)0000-0003-4071-1467 1003 027 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Anatom.Embriol.Humana 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 17, 5 (2025), 760 [20 pp.] Cancers Cancers 2072-6694 831630 http://zaguan.unizar.es/record/153135/files/texto_completo.pdf Versión publicada 2588718 http://zaguan.unizar.es/record/153135/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:153135 articulos driver 2025-10-17-14:32:39 ARTICLE