Akademik Veri Yönetim Sistemi
Expert Review of Anticancer Therapy, 2025 (SCI-Expanded, Scopus)
Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have markedly improved clinical outcomes and are the preferred first-line treatment for metastatic hormone receptor–positive breast cancer. However, acquired resistance is almost universal, leading to a critical need for effective strategies in the post-CDK4/6i setting. Areas covered: This review summarizes therapeutic approaches investigated after progression on CDK4/6i plus endocrine therapy. Key therapeutic approaches in this setting focus on overcoming resistance by inhibiting pathways such as PI3K/AKT/mTOR, altering treatment class through switching CDK4/6 inhibitors or endocrine therapy agents, and incorporating selective estrogen receptor degraders (SERDs). In addition, several novel strategies are under investigation, including targeting CDK7, utilizing antibody–drug conjugates, and exploiting DNA repair vulnerabilities with poly (ADP-ribose) polymerase (PARP) inhibitors. We conducted a literature search in PubMed/MEDLINE, Embase, and Scopus for studies published between January 2018 and June 2025 to identify evidence on efficacy, safety, and patient selection in this setting. Expert opinion: Therapeutic development for post-CDK4/6i metastatic HR+ breast cancer is evolving rapidly. Identifying molecular drivers of resistance and matching patients to targeted therapies will be essential to optimize outcomes. Continued efforts toward biomarker-based treatment selection and rational sequencing strategies are expected to refine post-CDK4/6i management.