ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 2 of them syntheses that pooled it.
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Who cites it
161 citing papers in PubMed, 2 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- Pooled it
- Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis.Prostate cancer and prostatic diseases · 2015Pooled it
- Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial.The Laryngoscope · 2017Trial
- Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer.Molecular oncology · 2014Trial
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- Identification of high-risk patients and metastatic progression in primary c/pN0 oral squamous cell carcinoma.Medicina oral, patologia oral y cirugia bucal · 2026Article
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- Primary Intracranial Squamous Cell Carcinoma Arising from an Epidermoid Cyst: Successful Management with Subtotal Resection and Gamma Knife Radiosurgery in an Elderly Patient.Current oncology (Toronto, Ont.) · 2026Article
- New cell lines expanding the diversity of Ewing sarcoma models.International journal of cancer · 2026Article
- Understanding the Tumor Microenvironment and Therapy Resistance in Head and Neck Squamous Cell Carcinoma.Cells · 2025Review
- Current and Emerging Protein Biomarkers for the Diagnosis and Prognosis of Head and Neck Cancer.Genes · 2025Review
- Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control.International journal of pharmaceutics: X · 2025Review
- Immune Evasion in Head and Neck Squamous Cell Carcinoma: Roles of Cancer-Associated Fibroblasts, Immune Checkpoints, andCancers · 2025Review
- Review
- Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.Journal of translational medicine · 2025Article
- Parameningeal embryonal rhabdomyosarcoma with leptomeningeal metastasis in a young adult female: illustrative case.Journal of neurosurgery. Case lessons · 2025Article
- Radiotherapy-Associated Cellular Senescence and EMT Alterations Contribute to Distinct Disease Relapse Patterns in Locally Advanced Cervical Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells.Oncotarget · 2025Article
- Radiosensitizing Effects of Metformin on Ionizing Irradiation: An Overview of Animal and Clinical Studies.Current drug research reviews · 2025Review
- Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases.Cell death discovery · 2024Review
101 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMortality of patients with head and neck squamous cell carcinoma (HNSCC) is primarily driven by tumor cell radioresistance leading to locoregional recurrence (LRR). In this study, we use a classification of TP53 mutation (disruptive vs. nondisruptive) and examine impact on clinical outcomes and radiation sensitivity. EXPERIMENTAL
designSeventy-four patients with HNSCC treated with surgery and postoperative radiation and 38 HNSCC cell lines were assembled; for each, TP53 was sequenced and the in vitro radioresistance measured using clonogenic assays. p53 protein expression was inhibited using short hairpin RNA (shRNA) and overexpressed using a retrovirus. Radiation-induced apoptosis, mitotic cell death, senescence, and reactive oxygen species (ROS) assays were carried out. The effect of the drug metformin on overcoming mutant p53-associated radiation resistance was examined in vitro as well as in vivo, using an orthotopic xenograft model.
resultsMutant TP53 alone was not predictive of LRR; however, disruptive TP53 mutation strongly predicted LRR (P = 0.03). Cell lines with disruptive mutations were significantly more radioresistant (P < 0.05). Expression of disruptive TP53 mutations significantly decreased radiation-induced senescence, as measured by SA-β-gal staining, p21 expression, and release of ROS. The mitochondrial agent metformin potentiated the effects of radiation in the presence of a disruptive TP53 mutation partially via senescence. Examination of our patient cohort showed that LRR was decreased in patients taking metformin.
conclusionsDisruptive TP53 mutations in HNSCC tumors predicts for LRR, because of increased radioresistance via the inhibition of senescence. Metformin can serve as a radiosensitizer for HNSCC with disruptive TP53, presaging the possibility of personalizing HNSCC treatment.
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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 OpenQuestion graph.