ArticleMolecular cancer2025
EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC.Oncoimmunology · 2026Article
- CircPRKCA Promotes NSCLC Progression via miR-200b-3p/FRMD6/SNAI2 Axis.International journal of molecular sciences · 2026Article
- Spatial transcriptomics reveals a molecular tumor budding signature in head and neck cancer.Genome medicine · 2026Article
- In-Solution Characterization of Extracellular Vesicles: A New Approach to Evaluating Antibody Binding and Surface Interactions.Journal of extracellular vesicles · 2026Article
- Identification of core cytotoxic T lymphocyte-related subtypes, establishment of a prognostic model, and analysis tumor microenvironment infiltration in HNSC.Scientific reports · 2026Article
- Personalized ctDNA analysis for detection of residual disease and recurrence in surgically treated HNSCC patients.NPJ precision oncology · 2026Article
- Diagnostic, Prognostic, and Predictive Molecular Biomarkers in Head and Neck Squamous Cell Carcinoma: A Comprehensive Review.Journal of clinical medicine · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4/6 Inhibition and Resistance to Immunotherapy in Breast Cancer.The breast journal · 2026Article
- Article
- Development of a cancer metastasis-associated risk model via multi-machine-learning algorithms for prognostic risk evaluation and clinical application in oral squamous cell carcinoma.Journal of translational medicine · 2025Article
- Long-term nutrition therapy leads to survival benefit in head and neck cancer patients receiving targeted or immunotherapy. A retrospective cohort study with real-world data.Frontiers in oncology · 2025Article
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Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) is a severe, frequently lethal condition. Oncogene addiction to epidermal growth factor receptor (EGFR) is a hallmark of HNSCC, but the clinical efficacy of EGFR-targeted therapies remains low. Understanding molecular networks governing EGFR-driven progression is paramount to the exploration of (co)-treatment targets and predictive markers.
methodsWe performed function-based mapping of differentially expressed genes in EGFR-mediated local invasion (fDEGs) using photoconvertible tracers and RNA-sequencing (RNA-seq) in a cellular 3D-model.
resultsUpon alignment with public single-cell RNA-seq (scRNA-seq) datasets and HNSCC-specific regulons, a gene regulatory network of local invasion (invGRN) was inferred from gene expression data, which was overrepresented in budding tumors. InvGRN comprises the central hubs inhibin subunit beta alpha (INHBA) and snail family transcriptional repressor 2 (SNAI2), and druggable fDEGs integrin subunit beta 4 (ITGB4), laminin 5 (LAMB3/LAMC2), and sphingosine kinase 1 (SPHK1). Blockade of INHBA repressed local invasion and was reverted by activin A, laminin 5, and sphingosine-1-phosphate, demonstrating a functional interconnectivity of the invGRN. Epithelial-to-mesenchymal transition (EMT) of malignant cells and the invGRN are induced by newly defined EGFR-activity subtypes with prognostic value that are promoted by amphiregulin (AREG) and epiregulin (EREG). Importantly, co-inhibition of SPHK1 showed synthetic effects on Cetuximab-mediated invasion blockade and high expression of selected fDEGs was associated with response to Cetuximab in patient-derived xenotransplantation (PDX) and R/M-HNSCC patients.
conclusionsWe describe an actionable network of EGFR-mediated local invasion and define druggable effectors with predictive potential regarding the response of R/M-HNSCC to Cetuximab.
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