ArticleBMC cancer2022
AXL regulates neuregulin1 expression leading to cetuximab resistance in head and neck cancer.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 14 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- The SPA17-AXL axis drives melanoma aggressiveness and SPA17-targeting vaccination exhibits antitumor efficacy.Frontiers in immunology · 2026Article
- In vitro synergistic effect of AXL, FAK and ErbB receptors inhibitors for head and neck cancer.Biology direct · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Tumor-associated MerTK promotes a pro-inflammatory microenvironment and enhances immune checkpoint inhibitor response in triple-negative breast cancer.Frontiers in oncology · 2025Article
- Nano-Biomechanical Investigation of Phosphatidylserine-Mediated Ebola Viral Attachment via Human Gas6 and Axl.Viruses · 2024Article
- Disrupting EGFR-HER2 Transactivation by Pertuzumab in HER2-Positive Cancer: Quantitative Analysis Reveals EGFR Signal Input as Potential Predictor of Therapeutic Outcome.International journal of molecular sciences · 2024Article
- MerTK Drives Proliferation and Metastatic Potential in Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Decoding the research landscape of drug resistance and therapeutic approaches in head and neck cancer: a bibliometric analysis from 2000 to 2023.Frontiers in pharmacology · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- AXL in cancer: a modulator of drug resistance and therapeutic target.Journal of experimental & clinical cancer research : CR · 2023Review
- A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.International journal of molecular sciences · 2023Article
- Targeting HER3-dependent activation of nuclear AKT improves radiotherapy of non-small cell lung cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR) is overexpressed and an important therapeutic target in Head and Neck cancer (HNC). Cetuximab is currently the only EGFR-targeting agent approved by the FDA for treatment of HNC; however, intrinsic and acquired resistance to cetuximab is a major problem in the clinic. Our lab previously reported that AXL leads to cetuximab resistance via activation of HER3. In this study, we investigate the connection between AXL, HER3, and neuregulin1 (NRG1) gene expression with a focus on understanding how their interdependent signaling promotes resistance to cetuximab in HNC.
methodsPlasmid or siRNA transfections and cell-based assays were conducted to test cetuximab sensitivity. Quantitative PCR and immunoblot analysis were used to analyze gene and protein expression levels. Seven HNC patient-derived xenografts (PDXs) were evaluated for protein expression levels.
resultsWe found that HER3 expression was necessary but not sufficient for cetuximab resistance without AXL expression. Our results demonstrated that addition of the HER3 ligand NRG1 to cetuximab-sensitive HNC cells leads to cetuximab resistance. Further, AXL-overexpressing cells regulate NRG1 at the level of transcription, thereby promoting cetuximab resistance. Immunoblot analysis revealed that NRG1 expression was relatively high in cetuximab-resistant HNC PDXs compared to cetuximab-sensitive HNC PDXs. Finally, genetic inhibition of NRG1 resensitized AXL-overexpressing cells to cetuximab.
conclusionsThe results of this study indicate that AXL may signal through HER3 via NRG1 to promote cetuximab resistance and that targeting of NRG1 could have significant clinical implications for HNC therapeutic approaches.
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.