ArticleCancer research2018
BET Inhibition Overcomes Receptor Tyrosine Kinase-Mediated Cetuximab Resistance in HNSCC.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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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
63 citing papers in PubMed, 101 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- EphA2/SHP2/SOX8 Axis: A Novel Target for Regulation of Migration and Cetuximab Treatment Sensitivity in Oral Squamous Cell Carcinoma.Molecular carcinogenesis · 2026Article
- Histone Deacetylase Inhibitor Panobinostat Augments the Antitumor Efficacy of Bromodomain Inhibitor JQ1 by Hijacking Mechanisms of Apoptosis in Head Neck Squamous Cell Carcinoma.Cell biochemistry and biophysics · 2026Article
- Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC.iScience · 2025Article
- Effectiveness of PROTAC BET Degraders in Combating Cisplatin Resistance in Head and Neck Cancer Cells.International journal of molecular sciences · 2025Article
- [Research progress on the mechanisms of resistance to cetuximab targeted therapy in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.Cancer science · 2025Article
- Advances in the study of posttranslational modifications of histones in head and neck squamous cell carcinoma.Clinical epigenetics · 2024Review
- HNCDrugResDb: a platform for deciphering drug resistance in head and neck cancers.Scientific reports · 2024Article
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.NPJ precision oncology · 2024Article
- Epigenetic regulation in cancer.MedComm · 2024Review
- Histone modifications in head and neck squamous cell carcinoma.Frontiers in oncology · 2024Review
- Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant Cancers.Research square · 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
- Negative correlation between acetyl-CoA acyltransferase 2 and cetuximab resistance in colorectal cancer.Acta biochimica et biophysica Sinica · 2023Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK. Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models. We hypothesized that, in HNSCC, targeting BRD4 could overcome cetuximab resistance by depleting alternative RTK expression. We generated independent models of cetuximab resistance in HNSCC cell lines and interrogated their RTK and BRD4 expression profiles. Cetuximab-resistant clones displayed increased expression and activation of several RTK, such as MET and AXL, as well as an increased percentage of BRD4-expressing cells. Both genetic and pharmacologic inhibition of BRD4 abrogated cell viability in models of acquired and intrinsic cetuximab resistance and was associated with a robust decrease in alternative RTK expression by cetuximab. Combined treatment with cetuximab and bromodomain inhibitor JQ1 significantly delayed acquired resistance and RTK upregulation in patient-derived xenograft models of HNSCC. These findings indicate that the combination of cetuximab and bromodomain inhibition may be a promising therapeutic strategy for patients with HNSCC.
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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.