ArticleJournal of the National Cancer Institute2015
Estrogen receptor mutations found in breast cancer metastases integrated with the molecular pharmacology of selective ER modulators.
Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- A NovelMicroorganisms · 2023Article
- Circulating tumour cells in the -omics era: how far are we from achieving the 'singularity'?British journal of cancer · 2022Review
- Estrogen Receptor and the Unfolded Protein Response: Double-Edged Swords in Therapy for Estrogen Receptor-Positive Breast Cancer.Targeted oncology · 2022Review
- Challenging Approach to the Development of Novel Estrogen Receptor Modulators Based on the Chemical Properties of Guaiazulene.International journal of molecular sciences · 2022Article
- Estrogen Receptor Complex to Trigger or Delay Estrogen-Induced Apoptosis in Long-Term Estrogen Deprived Breast Cancer.Frontiers in endocrinology · 2022Review
- CHRNA5 belongs to the secondary estrogen signaling network exhibiting prognostic significance in breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer.Molecular cancer therapeutics · 2021Article
- Dynamics Insights Into the Gain of Flexibility by Helix-12 in ESR1 as a Mechanism of Resistance to Drugs in Breast Cancer Cell Lines.Frontiers in molecular biosciences · 2019Article
- New insights into acquired endocrine resistance of breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Successful Targeted Therapies for Breast Cancer: the Worcester Foundation and Future Opportunities in Women's Health.Endocrinology · 2018Review
- Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.Nature reviews. Cancer · 2018Review
- A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers.Endocrine-related cancer · 2018Review
- A Computational Assay of Estrogen Receptor α Antagonists Reveals the Key Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers.Scientific reports · 2018Article
- Detection of Activating Estrogen Receptor Gene (Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- ERpS294 is a biomarker of ligand or mutational ERα activation and a breast cancer target for CDK2 inhibition.Oncotarget · 2017Article
- Targeting metastasis.Nature reviews. Cancer · 2016Review
- The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy.Molecular and cellular endocrinology · 2015Review
- Roles for miRNAs in endocrine resistance in breast cancer.Endocrine-related cancer · 2015Review
- Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients.OncoTargets and therapy · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The consistent reports of mutations at Asp538 and Tyr537 in helix 12 of the ligand-binding domain (LBD) of estrogen receptors (ERs) from antihormone-resistant breast cancer metastases constitute an important advance. The mutant amino acids interact with an anchor amino acid, Asp351, to close the LBD, thereby creating a ligand-free constitutively activated ER. Amino acids Asp 538, Tyr 537, and Asp 351 are known to play a role in either the turnover of ER, the antiestrogenic activity of the ER complex, or the estrogen-like actions of selective ER modulators. A unifying mechanism of action for these amino acids to enhance ER gene activation and growth response is presented. There is a range of mutations described in metastases vs low to zero in primary disease, so the new knowledge is of clinical relevance, thereby confirming an additional mechanism of acquired resistance to antihormone therapy through cell population selection pressure and enrichment during treatment. Circulating tumor cells containing ER mutations can be cultured ex vivo, and tumor tissues can be grown as patient-derived xenografts to add a new dimension for testing drug susceptibility for future drug discovery.
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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.