ArticleOncogene2022
Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- ESR1 mutations are associated with enhanced MTORC1 signaling in a context-dependent manner.Communications biology · 2026Article
- Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.Journal of applied toxicology : JAT · 2026Article
- Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition.Chemical biology & drug design · 2026Article
- Sakuranetin modulates estrogen receptor signaling in breast cancer cells.Journal of functional foods · 2026Article
- Distinct 2-phenylimidazo[1,2-iScience · 2026Article
- Activating mutations in ESR1 contribute to an immunosuppressive breast tumor microenvironment by dampening cytokine secretion.JCI insight · 2026Article
- Evaluating the clinical utility of ctDNA testing to identify molecular cancer progression - lessons from SERENA-6.NPJ breast cancer · 2026Article
- The natural L370F ERα variant confers endocrine resistance and sensitivity to ATRA in metastatic breast cancer cells.Cell communication and signaling : CCS · 2026Article
- Review
- Pharmacologic targeting of midasin (MDN1) reveals a potential therapeutic vulnerability in ESR1-mutant breast cancer.Frontiers in pharmacology · 2026Article
- A ternary switch model governing ERα ligand binding domain conformation.Nature communications · 2025Article
- In Silico Characterization of PathogenicGenes · 2025Article
- Circulating Tumor DNA Genotyping of Intrinsic and Acquired Gene Alterations in Patients With Advanced Breast Cancer Receiving Palbociclib: Biomarker Results From POLARIS Study.JCO precision oncology · 2025Article
- Why do we continue to have an incomplete understanding of estrogen receptor(s) actions in cancer systems?Endocrine-related cancer · 2025Review
- The Use of Next-Generation Sequencing in Personalized Medicine.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Discovering mechanisms of human genetic variation and controlling cell states at scale.Trends in genetics : TIG · 2024Review
- Loss of Hormone Receptor Expression after Exposure to Fluid Shear Stress in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.Endocrinology · 2024Article
- Selective impact of ALK and MELK inhibition on ERα stability and cell proliferation in cell lines representing distinct molecular phenotypes of breast cancer.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in the estrogen receptor (ESR1) gene are common in ER-positive breast cancer patients who progress on endocrine therapies. Most mutations localise to just three residues at, or near, the C-terminal helix 12 of the hormone binding domain, at leucine-536, tyrosine-537 and aspartate-538. To investigate these mutations, we have used CRISPR-Cas9 mediated genome engineering to generate a comprehensive set of isogenic mutant breast cancer cell lines. Our results confirm that L536R, Y537C, Y537N, Y537S and D538G mutations confer estrogen-independent growth in breast cancer cells. Growth assays show mutation-specific reductions in sensitivities to drugs representing three classes of clinical anti-estrogens. These differential mutation- and drug-selectivity profiles have implications for treatment choices following clinical emergence of ER mutations. Our results further suggest that mutant expression levels may be determinants of the degree of resistance to some anti-estrogens. Differential gene expression analysis demonstrates up-regulation of estrogen-responsive genes, as expected, but also reveals that enrichment for interferon-regulated gene expression is a common feature of all mutations. Finally, a new gene signature developed from the gene expression profiles in ER mutant cells predicts clinical response in breast cancer patients with ER mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.