ArticleCancer research2013
GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Window-of-opportunity Study of Single Agent Lenvatinib in Estrogen Receptor Positive Early Stage Breast Cancer
A Phase II Randomized Trial of Lenvatinib Combined With Letrozole Versus Fulvestrant in Metastatic Estrogen Receptor (ER) Positive, HER2 Negative Breast Cancer, Who Have Progressed on First-line Aromatase Inhibitor + a CDK4/6 Inhibitor.
Who cites it
69 citing papers in PubMed, 116 citations in OpenAlex.
- Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients.Breast cancer research : BCR · 2019Trial
- Transcriptome Alterations in Liver Metastases of Colorectal Cancer After Acquired Resistance to Cetuximab.Cancer genomics & proteomicsTrial
- New perspectives on endocrine therapy suitability for hormone receptor-positive metastatic breast cancer in clinical practice.Breast (Edinburgh, Scotland) · 2026Review
- Kinase Plasticity with Vandetanib Treatment Enhances Sensitivity to Tamoxifen in Estrogen Receptor Positive Breast Cancer.Molecular cancer therapeutics · 2026Article
- RET signaling as a mediator of estrogen receptor positive breast cancer brain metastasis.Communications biology · 2026Article
- Endocrine Resistance Score Based on Three Key Genes Predicts Prognosis and Reveals Potential Therapeutic Targets for ER+HER2- Breast Cancer.Cell proliferation · 2026Article
- Transcriptome study exploring the mechanisms linking pollutants and breast cancer aggressiveness.Scientific reports · 2025Article
- Integrating neuroscience and oncology: neuroimmune crosstalk in the initiation and progression of digestive system tumors.Molecular cancer · 2025Review
- Molecular classification of hormone receptor-positive /HER2-positive breast cancer reveals potential neoadjuvant therapeutic strategies.Signal transduction and targeted therapy · 2025Article
- Radiogenomic Landscape of Metastatic Endocrine-Positive Breast Cancer Resistant to Aromatase Inhibitors.Cancers · 2025Review
- Thyroid C-Cell Biology and Oncogenic Transformation.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Germline sequence variation in cancer genes in Rwandan breast and prostate cancer cases.NPJ genomic medicine · 2024Article
- RET overexpression leads to increased brain metastatic competency in luminal breast cancer.Journal of the National Cancer Institute · 2024Article
- RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer.Frontiers in oncology · 2024Article
- REThinking the role of the RET oncogene in breast cancer.Frontiers in oncology · 2024Review
- Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer.Cancer research · 2023Article
- Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.Biochemical pharmacology · 2023Review
- Article
- A network map of GDNF/RET signaling pathway in physiological and pathological conditions.Journal of cell communication and signaling · 2023Article
- Desmocollin-1 is associated with pro-metastatic phenotype of luminal A breast cancer cells and is modulated by parthenolide.Cellular & molecular biology letters · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine therapy for postmenopausal women with ER(+) breast cancers. Despite providing substantial improvements in patient outcome, aromatase inhibitor resistance remains a major clinical challenge. The receptor tyrosine kinase, RET, and its coreceptor, GFRα1, are upregulated in a subset of ER(+) breast cancers, and the RET ligand, glial-derived neurotrophic factor (GDNF) is upregulated by inflammatory cytokines. Here, we report the findings of a multidisciplinary strategy to address the impact of GDNF-RET signaling in the response to aromatase inhibitor treatment. In breast cancer cells in two-dimensional and three-dimensional culture, GDNF-mediated RET signaling is enhanced in a model of aromatase inhibitor resistance. Furthermore, GDNF-RET signaling promoted the survival of aromatase inhibitor-resistant cells and elicited resistance in aromatase inhibitor-sensitive cells. Both these effects were selectively reverted by the RET kinase inhibitor, NVP-BBT594. Gene expression profiling in ER(+) cancers defined a proliferation-independent GDNF response signature that prognosed poor patient outcome and, more importantly, predicted poor response to aromatase inhibitor treatment with the development of resistance. We validated these findings by showing increased RET protein expression levels in an independent cohort of aromatase inhibitor-resistant patient specimens. Together, our results establish GDNF-RET signaling as a rational therapeutic target to combat or delay the onset of aromatase inhibitor resistance in breast cancer.
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What OpenQuestion holds
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.