ArticleBritish journal of cancer2020
Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines.
Article in British journal of cancer, 2020. 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 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Integration of Bulk and Single-Cell RNA Sequencing Analyses in Biomedicine.International journal of molecular sciences · 2026Review
- scDrugAtlas: an integrative single-cell drug response database for dissecting tumour heterogeneity in therapeutic efficacy.Database : the journal of biological databases and curation · 2026Article
- Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC.iScience · 2025Article
- Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).Oncology reports · 2024Review
- Clinical and genomic characterization of chemoradiation-resistant HPV-positive oropharyngeal squamous cell carcinoma.Frontiers in oncology · 2024Article
- DELFOS-drug efficacy leveraging forked and specialized networks-benchmarking scRNA-seq data in multi-omics-based prediction of cancer sensitivity.Bioinformatics (Oxford, England) · 2023Article
- Application of single-cell RNA sequencing in head and neck squamous cell carcinoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- TFAP2A promotes cervical cancer via a positive feedback pathway with PD‑L1.Oncology reports · 2023Article
- ICAT: a novel algorithm to robustly identify cell states following perturbations in single-cell transcriptomes.Bioinformatics (Oxford, England) · 2023Article
- Multiomics Empowers Predictive Pancreatic Cancer Immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer.Molecular cancer · 2022Article
- Model-informed experimental design recommendations for distinguishing intrinsic and acquired targeted therapeutic resistance in head and neck cancer.NPJ systems biology and applications · 2022Article
- Article
- OBIF: an omics-based interaction framework to reveal molecular drivers of synergy.NAR genomics and bioinformatics · 2022Article
- Harnessing changes in open chromatin determined by ATAC-seq to generate insulin-responsive reporter constructs.BMC genomics · 2022Article
- Article
- RNA Sequencing and Cell Models of Virus-Associated Cancer (Review).Sovremennye tekhnologii v meditsine · 2022Review
- Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma.Frontiers in immunology · 2022Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIdentifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance.
methodsWe generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT).
resultsSingle-cell RNA-seq demonstrates heterogeneity, with cell-specific TFAP2A and VIM expression profiles in response to treatment and also with global changes to various signalling pathways. RNA-seq and ATAC-seq reveal global changes within 5 days of therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A expression is associated with HNSCC decreased growth, with cetuximab and JQ1 increasing the inhibitory effect. Regarding the EMT process, short-term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance.
conclusionOverall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumour cells are still sensitive to therapy.
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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 Socratic graph.