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简介:AbstractIncreasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
简介:AbstractNearly 70% of breast cancer (BC) is hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and endocrine therapy is the mainstay of treatment for this subtype. However, intrinsic or acquired endocrine resistance can occur during the endocrine treatment. Based on insights of endocrine resistance mechanisms, a number of targeted therapies have been and continue to be developed. With regard to HR-positive, HER2-negative advanced BC, aromatase inhibitor (AI) is superior to tamoxifen, and fulvestrant is a better option for patients previously exposed to endocrine therapy. Targeted drugs, such as cyclindependent kinases (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, and histone deacetylase (HDAC) inhibitors, play a significant role in the present and show a promising future. With the application of CDK4/6 inhibitors becoming common, mechanisms of acquired resistance to them should also be taken into consideration.