ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2017
Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors.
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Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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133citing papers in PubMed, 1 pooled it
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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
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Deciphering NOTCH1 as a Biomarker in Adenoid Cystic Carcinoma: Insights From a Systematic Review With Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025Pooled it
- Axitinib plus Avelumab in Recurrent/Metastatic Adenoid Cystic Carcinoma: Biomarker Analysis and Updated Results of the Phase II Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase 2 Trial of Regorafenib in Recurrent/Metastatic Adenoid Cystic Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial.Nature medicine · 2023Trial
- Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.Oncotarget · 2017Trial
- Clinicogenomic Features and Outcomes of Adenoid Cystic Carcinoma With Central Nervous System Metastases: A Single-Institution Cohort Study.Head & neck · 2026Article
- Integrating Histological and Molecular Findings for Practical Salivary Gland Diagnostics.Head and neck pathology · 2026Review
- AKT, ATR, and Notch Inhibitors Radiosensitize a Preclinical Model of Adenoid Cystic Carcinoma.Head & neck · 2026Article
- Article
- NOTCH1 acts as a tumor suppressor that induces early differentiation in head and neck cancer.JCI insight · 2026Article
- Article
- Prognostic impact of HLA class I immunohistochemistry staining intensity with regard to the risk of recurrence of adenoid cystic carcinoma.Molecular and clinical oncology · 2026Article
- Metastatic and recurrent salivary gland carcinoma: clinical characteristics and comprehensive molecular profiling at a tertiary care center.Journal of cancer research and clinical oncology · 2026Article
- Solid-variant primary pulmonary adenoid cystic carcinoma with pleural metastasis and malignant pleural effusion: a rare case report.Frontiers in oncology · 2026Article
- Case Report: A rare case of over 45 years' survival in a patient with tonsillar adenoid cystic carcinoma.Frontiers in oncology · 2026Article
- Multimodal treatment for multifocal metastatic maxillary adenoid cystic carcinoma: A case report.Oncology letters · 2025Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Integrative diagnostic approach to salivary gland tumors: from clinical evaluation to molecularly targeted therapy.Virchows Archiv : an international journal of pathology · 2025Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 1 institution in 1 country.
Renata FerrarottoRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Yoshitsugu MitaniRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Lixia DiaoRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Irene GuijarroRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Jing WangRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Patrick Zweidler-McKayRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Diana BellRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
William N WilliamRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Bonnie S GlissonRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Michael J WickRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Ann M KapounRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Amita PatnaikRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Gail EckhardtRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Pamela MunsterRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Leonardo FaoroRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Jakob DupontRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
J Jack LeeRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Andrew FutrealRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Adel K El-NaggarRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
John V HeymachRenata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William Jr, Bonnie S. Glisson, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, and John V. Heymach, University of Texas MD Anderson Cancer Center, Houston; Michael J. Wick and Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Ann M. Kapoun, Leonardo Faoro, and Jakob Dupont, OncoMed Pharmaceuticals, Redwood City; Pamela Munster, University of California San Francisco, San Francisco, CA; and Gail Eckhardt, University of Colorado Denver School of Medicine, Denver, CO.
Williams & Associates · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4MMolecular and Epidemiologic Characterization of Salivary Gland CarcinomasU01DE019765 · NIDCR · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EL-NAGGAR, ADEL K. · 2009 to 2013
$6.9MMarkers and therapeutic strategies for overcoming chemoradiotherapy resistanceR01CA168484 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HEYMACH, JOHN V. · 2011 to 2015
$1.4MNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA168484NIDCR NIH HHS U01 DE019765
Abstract
Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro. The Notch1 inhibitor brontictuzumab was tested in patient-derived xenografts from patients with ACC and in a patient with ACC who was enrolled in a phase I study. Results NOTCH1 mutations occurred predominantly (14 of 15 patients) in the negative regulatory region and Pro-Glu-Ser-Thr-rich domains, the same two hotspots seen in T-cell acute lymphoblastic leukemias, and led to pathway activation in vitro. NOTCH1-mutant tumors demonstrated significantly higher levels of Notch1 pathway activation than wild-type tumors on the basis of Notch1 intracellular domain staining ( P = .004). NOTCH1 mutations define a distinct aggressive ACC subgroup with a significantly higher likelihood of solid subtype ( P < .001), advanced-stage disease at diagnosis ( P = .02), higher rate of liver and bone metastasis ( P ≤ .02), shorter relapse-free survival (median, 13 v 34 months; P = .01), and shorter overall survival (median 30 v 122 months; P = .001) when compared with NOTCH1 wild-type tumors. Significant tumor growth inhibition with brontictuzumab was observed exclusively in the ACC patient-derived xenograft model that harbored a NOTCH1 activating mutation. Furthermore, an index patient with NOTCH1-mutant ACC had a partial response to brontictuzumab. Conclusion NOTCH1 mutations define a distinct disease phenotype characterized by solid histology, liver and bone metastasis, poor prognosis, and potential responsiveness to Notch1 inhibitors. Clinical studies targeting Notch1 in a genotype-defined ACC subgroup are warranted.
Indexed as
MutationAdultAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBone NeoplasmsCarcinoma, Adenoid CysticDisease-Free SurvivalDNA Mutational AnalysisFemaleGenetic Predisposition to DiseaseHEK293 CellsHumansImmunohistochemistryKaplan-Meier EstimateAntineoplastic AgentsBiomarkers, TumorNOTCH1 protein, humanReceptor, Notch1
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