ArticlePloS one2013
High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck.
Article in PloS one, 2013. 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 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 70 citations in OpenAlex.
- Trial
- HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors.Future oncology (London, England) · 2025Article
- NOTCH1 signaling promotes protein stability of HER3 through the AKT pathway in squamous cell carcinoma of head and neck.Oncogenesis · 2021Article
- Review
- Thirty Years of HER3: From Basic Biology to Therapeutic Interventions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- Review
- CAN017, a novel anti-HER3 antibody, exerted great potency in mouse avatars of esophageal squamous cell carcinoma with NRG1 as a biomarker.American journal of cancer research · 2021Article
- Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance.Molecular cancer therapeutics · 2019Review
- Aberrant HER3 ligand heregulin-expressing head and neck squamous cell carcinoma is resistant to anti-EGFR antibody cetuximab, but not second-generation EGFR-TKI.Oncogenesis · 2019Article
- Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer.Experimental & molecular medicine · 2019Review
- NRG-1 Stimulates Serum DJ-1 Increase in Breast Cancers.Pathology oncology research : POR · 2019Article
- Translation and evaluation of a pre-clinical 5-protein response prediction signature in a breast cancer phase Ib clinical trial.PloS one · 2019Article
- HER3 signaling and targeted therapy in cancer.Oncology reviews · 2018Article
- Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.Cell death & disease · 2018Article
- An ERBB1-3 Neutralizing Antibody Mixture With High Activity Against Drug-Resistant HER2+ Breast Cancers With ERBB Ligand Overexpression.Journal of the National Cancer Institute · 2017Article
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
- ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC.PloS one · 2017Article
- Systems biology driving drug development: from design to the clinical testing of the anti-ErbB3 antibody seribantumab (MM-121).NPJ systems biology and applications · 2017Review
- Real-Time Reverse-Transcription Quantitative Polymerase Chain Reaction Assay Is a Feasible Method for the Relative Quantification of Heregulin Expression in Non-Small Cell Lung Cancer Tissue.Biomarker insights · 2017Article
- Novel association of DJ-1 with HER3 potentiates HER3 activation and signaling in cancer.Oncotarget · 2016Article
Corrections and comments
- Erratum issuedAnDo [corrected to Do, An]
Authors and funding
20 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTumors with oncogenic dependencies on the HER family of receptor tyrosine kinases (RTKs) often respond well to targeted inhibition. Our previous work suggested that many cell lines derived from squamous cell carcinomas of the head and neck (SCCHNs) depend on autocrine signaling driven by HER2/3 dimerization and high-level co-expression of HRG. Additionally, results from a Phase I trial of MEHD7495A, a dual-action antibody that blocks ligand binding to EGFR and HER3, suggest that high-level HRG expression was associated with clinical response in SCCHN patients. Here we explore the hypothesis that high-level HRG expression defines a subpopulation of SCCHNs with activated HER3. EXPERIMENTAL
designqRT-PCR expression profiling was performed on >750 tumors of diverse origin, including >150 therapy-naïve, primary, and recurrent SCCHNs. Activated HER3, defined by immunoprecipitation of phospho-HER3, was compared to HRG expression in SCCHN samples. Paracrine versus autocrine expression was evaluated using RNA-in situ hybridization.
resultsSCCHN tumors express the highest levels of HRG compared to a diverse collection of other tumor types. We show that high HRG expression is associated with activated HER3, whereas low HRG expression is associated with low HER3 activation in SCCHN tumors. Furthermore, HRG expression is higher in recurrent SCCHN compared to patient-matched therapy naïve specimens.
conclusionsHRG expression levels define a biologically distinct subset of SCCHN patients. We propose that high-level expression of HRG is associated with constitutive activation of HER3 in SCCHN and thus defines an actionable biomarker for interventions targeting HER3.
Indexed as
Identifiers
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.