Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations. In this review, we discuss the mechanisms of action and resistance to CDK4/6i, providing a comprehensive overview of emerging efficacy and safety data, biomarker-driven strategies, and ongoing clinical trials. Finally, we delineate key research priorities aimed at guiding the development of innovative therapeutic combinations.
Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies / Giugliano, F., De Angelis, C., Pistilli, B., Viale, G., Bianchini, G., Giuliano, M., Malorni, L., Taurelli Salimbeni, B., Esposito, A., Giordano, A., Yap, T.A., Curigliano, G., Criscitiello, C.. - In: CANCER TREATMENT REVIEWS. - ISSN 0305-7372. - 139:(2025). [10.1016/j.ctrv.2025.102980]
Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies
Viale, Giulia;Bianchini, Giampaolo;
2025-01-01
Abstract
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations. In this review, we discuss the mechanisms of action and resistance to CDK4/6i, providing a comprehensive overview of emerging efficacy and safety data, biomarker-driven strategies, and ongoing clinical trials. Finally, we delineate key research priorities aimed at guiding the development of innovative therapeutic combinations.| File | Dimensione | Formato | |
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