ArticleCancer research2017
Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Steroid receptor coactivators: from basic research to translational opportunities.Endocrine reviews · 2026Review
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6.NPJ breast cancer · 2026Article
- Resistance to FOXM1 inhibitors in breast cancer is accompanied by impeding ferroptosis and apoptotic cell death.Breast cancer research and treatment · 2024Article
- Steroid receptor coactivators in Treg and Th17 cell biology and function.Frontiers in immunology · 2024Review
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
- Therapeutic resistance to anti-oestrogen therapy in breast cancer.Nature reviews. Cancer · 2023Review
- Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.NPJ breast cancer · 2022Article
- Estrogen Receptor Beta 1: A Potential Therapeutic Target for Female Triple Negative Breast Cancer.Endocrinology · 2022Article
- Evolution of 3-(4-hydroxyphenyl)indoline-2-one as a scaffold for potent and selective anticancer activity.RSC medicinal chemistry · 2022Review
- Article
- Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.Journal of medicinal chemistry · 2022Article
- Steroid receptor coactivators - their role in immunity.Frontiers in immunology · 2022Review
- Transcription Regulation and Genome Rewiring Governing Sensitivity and Resistance to FOXM1 Inhibition in Breast Cancer.Cancers · 2021Article
- Prolactin and endocrine therapy resistance in breast cancer: The next potential hope for breast cancer treatment.Journal of cellular and molecular medicine · 2021Review
- Defining the Energetic Basis for a Conformational Switch Mediating Ligand-Independent Activation of Mutant Estrogen Receptors in Breast Cancer.Molecular cancer research : MCR · 2021Article
- A small-molecule activator of the unfolded protein response eradicates human breast tumors in mice.Science translational medicine · 2021Article
- The effect of protein mutations on drug binding suggests ensuing personalised drug selection.Scientific reports · 2021Article
- Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.Breast cancer research : BCR · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Many estrogen receptor α (ERα)-positive breast cancers develop resistance to endocrine therapy via mutation of ERs whose constitutive activation is associated with shorter patient survival. Because there is now a clinical need for new antiestrogens (AE) against these mutant ERs, we describe here our development and characterization of three chemically novel AEs that effectively suppress proliferation of breast cancer cells and tumors. Our AEs are effective against wild-type and Y537S and D538G ERs, the two most commonly occurring constitutively active ERs. The three new AEs suppressed proliferation and estrogen target gene expression in WT and mutant ER-containing cells and were more effective in D538G than in Y537S cells and tumors. Compared with WT ER, mutants exhibited approximately 10- to 20-fold lower binding affinity for AE and a reduced ability to be blocked in coactivator interaction, likely contributing to their relative resistance to inhibition by AE. Comparisons between mutant ER-containing MCF7 and T47D cells revealed that AE responses were compound, cell-type, and ERα-mutant dependent. These new ligands have favorable pharmacokinetic properties and effectively suppressed growth of WT and mutant ER-expressing tumor xenografts in NOD/SCID-γ mice after oral or subcutaneous administration; D538G tumors were more potently inhibited by AE than Y537S tumors. These studies highlight the differential responsiveness of the mutant ERs to different AEs and make clear the value of having a toolkit of AEs for treatment of endocrine therapy-resistant tumors driven by different constitutively active ERs.
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