ArticleBritish journal of cancer2021
RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer.Cancer research · 2026Article
- Discovery of a novel small molecule degrader of wild type and mutant estrogen receptors using DNA encoded libraries.NPJ breast cancer · 2025Article
- Targeting Resistance Pathways in Breast Cancer Through Precision Oncology: Nanotechnology and Immune Modulation Approaches.Biomedicines · 2025Review
- Role of Mesenchymal Markers in Colorectal Cancer Metastasis.Molecular biology reports · 2025Review
- Organoids in breast cancer translational research: intersection of technologies.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- Review
- PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer.Molecular cancer therapeutics · 2024Article
- Identification of modules and key genes associated with breast cancer subtypes through network analysis.Scientific reports · 2024Article
- Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling.Scientific reports · 2024Article
- Small-molecule agents for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer.Molecular cancer research : MCR · 2023Article
- Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity.Molecular cell · 2023Article
- Review
- Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib.Frontiers in pharmacology · 2023Review
- Assessment of durable chemoimmunotherapy response via circulating tumor DNA in advanced esophageal squamous cell carcinoma.Thoracic cancer · 2022Article
- An immune-humanized patient-derived xenograft model of estrogen-independent, hormone receptor positive metastatic breast cancer.Breast cancer research : BCR · 2021Article
- Understanding breast cancer heterogeneity through non-genetic heterogeneity.Breast cancer (Tokyo, Japan) · 2021Review
- MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase.Journal of oncology · 2021Article
- Laboratory Models for Investigating Breast Cancer Therapy Resistance and Metastasis.Frontiers in oncology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.
methodsWe performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells. We validated Recepteur d'Origine Nantais (RON) and PI3K hyperactivity through phospho-immunoblot analysis, organoid growth assays, and in an in vivo patient-derived xenograft (PDX) metastatic model.
resultsWe demonstrated that RON was hyperactivated in ESR1 mutant models, and in acquired palbociclib-resistant (PalbR) models. RON and insulin-like growth factor 1 receptor (IGF-1R) interacted as shown through pharmacological and genetic inhibition and were regulated by the mutant ER as demonstrated by reduced phospho-protein expression with endocrine therapies (ET). We show that ET in combination with a RON inhibitor (RONi) decreased ex vivo organoid growth of ESR1 mutant models, and as a monotherapy in PalbR models, demonstrating its therapeutic efficacy. Significantly, ET in combination with the RONi reduced metastasis of an ESR1 Y537S mutant PDX model.
conclusionsOur results demonstrate that RON/PI3K pathway inhibition may be an effective treatment strategy in ESR1 mutant and PalbR MBC patients. Clinically our data predict that ET resistance mechanisms can also contribute to CDK4/6 inhibitor resistance.
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