ArticleThe Journal of clinical investigation2015
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.Nature medicine · 2025Trial
- The women in steady exercise research (WISER) survivor trial: The innovative transdisciplinary design of a randomized controlled trial of exercise and weight-loss interventions among breast cancer survivors with lymphedema.Contemporary clinical trials · 2017Trial
- Translational issues with phototherapy of cancer.Translational oncology · 2026Review
- Notch signaling regulates the secretion of pro-metastatic factors in extracellular vesicles in liposarcoma.Cancer letters · 2026Article
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Intracellular lipid droplets positively regulate the dormancy of colorectal cancer cells depending on ELF1-ACSL5 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer.Nature communications · 2026Article
- Review
- The Lymphatic-Bone Axis in Cancer Metastasis.Cancers · 2026Review
- Epitranscriptomics as a Candidate Universal Modulator of Dormancy Transitions.Ecology and evolution · 2026Review
- Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.The FEBS journal · 2025Article
- The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.Journal of bone oncology · 2025Review
- DTC-Flow: a flow cytometry-based detection platform for characterizing bone marrow disseminated tumor cells in breast cancer.NPJ breast cancer · 2025Article
- CD44 Marks Dormant Tumor Cells After HER2 Inhibition in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Search for Mutations Connected With Non-Response to Anti-EGFR Therapy in mCRC in the Morphologically Defined Regions of Primary Tumours.Cancer medicine · 2025Article
- Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence.Military Medical Research · 2025Review
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- Exosomal miR-182-5p from breast cancer cells reprogram tumor-associated macrophages and promote triple-negative breast cancer progression by targeting Notch1 in macrophages.Archives of medical science : AMS · 2025Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Breast cancer mortality is principally due to recurrent tumors that arise from a reservoir of residual tumor cells that survive therapy. Remarkably, breast cancers can recur after extended periods of clinical remission, implying that at least some residual tumor cells pass through a dormant phase prior to relapse. Nevertheless, the mechanisms that contribute to breast cancer recurrence are poorly understood. Using a mouse model of recurrent mammary tumorigenesis in combination with bioinformatics analyses of breast cancer patients, we have identified a role for Notch signaling in mammary tumor dormancy and recurrence. Specifically, we found that Notch signaling is acutely upregulated in tumor cells following HER2/neu pathway inhibition, that Notch signaling remains activated in a subset of dormant residual tumor cells that persist following HER2/neu downregulation, that activation of Notch signaling accelerates tumor recurrence, and that inhibition of Notch signaling by either genetic or pharmacological approaches impairs recurrence in mice. Consistent with these findings, meta-analysis of microarray data from over 4,000 breast cancer patients revealed that elevated Notch pathway activity is independently associated with an increased rate of recurrence. Together, these results implicate Notch signaling in tumor recurrence from dormant residual tumor cells and provide evidence that dormancy is a targetable stage of breast cancer progression.
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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.