ArticleOncotarget2017
Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment.Current issues in molecular biology · 2025Review
- Review
- Synthesis and Biological Evaluation of Novel Cationic Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivative for Epidermal Growth Factor Receptor Targeting.Pharmaceutics · 2024Article
- Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers.Journal of cancer research and clinical oncology · 2023Review
- Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance.Stem cell reviews and reports · 2023Review
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Immunology of Oral Squamous Cell Carcinoma-A Comprehensive Insight with Recent Concepts.Life (Basel, Switzerland) · 2022Review
- Review
- Reply.Cancer letters · 2022Article
- NSAIDs OvercomeCancers · 2022Article
- Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Afatinib induces pro-survival autophagy and increases sensitivity to apoptosis in stem-like HNSCC cells.Cell death & disease · 2021Article
- High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma.Scientific reports · 2021Article
- Dual blockade of EGFR and CDK4/6 delays head and neck squamous cell carcinoma progression by inducing metabolic rewiring.Cancer letters · 2021Article
- Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance.Clinical epigenetics · 2021Review
- Oral Cancer Stem Cells: Therapeutic Implications and Challenges.Frontiers in oral health · 2021Review
- Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy.Therapeutic advances in medical oncology · 2021Review
- Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis.Oncogene · 2021Article
- Anti-EGFR treatment effects on laryngeal cancer stem cells.American journal of translational research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.
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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.