ArticleBreast cancer research : BCR2021
Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer.
Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Abemaciclib in HR+, HER2- Breast Cancer: A Narrative Review of the Clinical Evidence.Oncology and therapy · 2026Review
- Molecular Mechanisms Underlying Recurrence in Triple-Positive Breast Cancer (ER+/PR+/HER2+) and Potential Repurposing of Multi-Target Inhibitors.International journal of molecular sciences · 2026Review
- Loss of luminal lineage drives resistance to next-generation ERα antagonists in pretreated ERNature communications · 2026Article
- Biomarkers of primary and secondary resistance to cyclin dependent kinases 4 and 6 inhibitors in metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- WEE1 inhibition delays resistance to CDK4/6 inhibitor and antiestrogen treatment in ER+ MCF7 cells.NPJ systems biology and applications · 2025Article
- H3K27me3 chromatin heterogeneity reveals variable cell responses to estrogen and endocrine treatment.bioRxiv : the preprint server for biology · 2025Article
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Article
- Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.International journal of molecular sciences · 2025Article
- Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance.Molecular oncology · 2025Article
- Analysis of the Main Directions in the Development of Mono and Combination Pharmacotherapy Acting on Hormonal Signaling Pathways of Breast Cancer According to the FDA Databases and Clinicaltrials.gov.Current medicinal chemistry · 2025Review
- Failure to progress: breast and prostate cancer cell lines in developing targeted therapies.Cancer metastasis reviews · 2024Review
- Mcam stabilizes a luminal progenitor-like breast cancer cell state via Ck2 control and Src/Akt/Stat3 attenuation.NPJ breast cancer · 2024Article
- Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer.Cancer chemotherapy and pharmacology · 2024Article
- Palbociclib sensitizes ER-positive breast cancer cells to fulvestrant by promoting the ubiquitin-mediated degradation of ER-α via SNHG17/Hippo-YAP axis.Breast cancer research and treatment · 2024Article
- Review
- Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.Frontiers in immunology · 2024Review
- Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer.Breast cancer research and treatment · 2024Article
- Characteristic Binding Landscape of Estrogen Receptor-α36 Protein Enhances Promising Cancer Drug Design.Biomolecules · 2023Article
- Modeling the novel SERD elacestrant in cultured fulvestrant-refractory HR-positive breast circulating tumor cells.Breast cancer research and treatment · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself.
methodsTo study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant.
resultsWe found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival.
conclusionsThese data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.
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