ArticleCancer letters2021
Dual blockade of EGFR and CDK4/6 delays head and neck squamous cell carcinoma progression by inducing metabolic rewiring.
Article in Cancer letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- ANP32E drives lung adenocarcinoma progression via GSK3β-mediated glycolytic reprogramming.Cell death & disease · 2026Article
- Multiplexed imaging mass cytometry elicits p-S6 as a therapeutic and prognostic factor in diffuse large B-cell lymphoma.Blood advances · 2025Article
- USP5 Promotes Head and Neck Squamous Cell Carcinoma Progression via mTOR Signaling Pathway.Cancer medicine · 2025Article
- Integrative analysis of m7G methylation-associated genes prognostic signature with immunotherapy and identification of LARP1 as a key oncogene in head and neck squamous cell carcinoma.Frontiers in immunology · 2025Article
- Cuproptosis-related lncRNA JPX regulates malignant cell behavior and epithelial-immune interaction in head and neck squamous cell carcinoma via miR-193b-3p/PLAU axis.International journal of oral science · 2024Article
- Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives.Redox biology · 2024Review
- Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma.Experimental & molecular medicine · 2024Article
- Palbociclib inhibits the progression of head and neck cancer and improves the Cetuximab response under specific condition in vitro and in vivo.Molecular biology reports · 2024Article
- Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy.Current issues in molecular biology · 2024Article
- Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice.Frontiers in pharmacology · 2024Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.Biomarker research · 2023Review
- Review
- Article
- Reply.Cancer letters · 2022Article
- The Renaissance of Cyclin Dependent Kinase Inhibitors.Cancers · 2022Review
- IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy.Frontiers in cell and developmental biology · 2022Review
- Current Status and Prospects of Clinical Treatment of Osteosarcoma.Technology in cancer research & treatmentReview
- Targeting the EGFR signaling pathway in cancer therapy: What's new in 2023?Expert opinion on therapeutic targetsReview
Corrections and comments
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- Commented on byReply.2022
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreER
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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.