Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.
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http://dx.doi.org/10.1007/s40265-024-02144-y | DOI Listing |
Breast Cancer
January 2025
Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Antibody-drug conjugates (ADCs) are an emerging class of anticancer therapy that combines the specificity and long circulation half-life of monoclonal antibodies with the cytotoxic potency of the payload connected through a chemical linker. The optimal management of toxicities is crucial for improving quality of life in patients undergoing ADCs and for avoiding improper dose reductions or discontinuations. This article focuses on the characteristics and management of nausea and vomiting (NV) induced by three ADCs: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd).
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Departments of Radiology and Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
Purpose: Trophoblast cell-surface antigen 2 (Trop2) is overexpressed in various solid tumors and contributes to tumor progression, while its expression remains low in normal tissues. Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan-hziy (Trodelvy), has shown efficacy in targeting this antigen. Leveraging the enhanced specificity of ADCs, we conducted the first immunoPET imaging study of Trop2 expression in gastric cancer (GC) and triple-negative breast cancer (TNBC) models using Zr-labeled Trodelvy ([Zr]Zr-DFO-Trodelvy).
View Article and Find Full Text PDFJ Gastroenterol
January 2025
Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Mol Biol Rep
January 2025
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Background: Breast carcinoma stands out as the most widespread invasive cancer and the top contributor to cancer-related mortality in women. Nanoparticles have emerged as promising tools in cancer detection, diagnosis, and prevention. In this study, the antitumor and apoptotic capability of silver nanoparticles synthesized through Scrophularia striata extract (AgNPs-SSE) was investigated toward breast cancer cells.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
January 2025
Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Purpose: Growing evidence suggests that the tyrosine phosphatase SHP2 is pivotal for tumor progression. Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, characterized by its high recurrence rate, aggressive metastasis, and resistance to chemotherapy. Understanding the mechanisms of tumorigenesis and the underlying molecular pathways in TNBC could aid in identifying new therapeutic targets.
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