ArticleCancer research2023
NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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.
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Who cites it
44 citing papers in PubMed, 51 citations in OpenAlex.
- Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.Targeted oncology · 2025Trial
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Article
- Hypoxia and Oxidation Pathway Crosstalk in Head and Neck Squamous Cell Carcinoma.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- Driving progress in recurrent and metastatic head and neck cancer: the NRG Oncology perspective.Journal of the National Cancer Institute · 2026Review
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- An exosome-biomimetic photothermal nanocarrier for IGF2BP2 siRNA delivery and enhanced ferroptosis in head and neck squamous cell carcinoma.Materials today. Bio · 2026Article
- IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- M2 macrophage related genes predict prognosis and drug response in prostate cancer.Discover oncology · 2026Article
- From metabolism to genome integrity: NRF2 as a key mediator of cancer therapy response.Frontiers in cell and developmental biology · 2026Review
- Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities.Translational oncology · 2026Article
- Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.Journal of Cancer · 2026Review
- Review
- Activating NRF2Cancer gene therapy · 2025Article
- From Carcinogenesis to Drug Resistance: The Multifaceted Role of Oxidative Stress in Head and Neck Cancer.Cancers · 2025Review
- NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting.Oncogene · 2025Review
- Nrf2 Hyperactivation as a Driver of Radiotherapy Resistance and Suppressed Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Oncogenic NFE2L2 mutations in plasma ctDNA and tumors are predictors and prognosticators of chemoradiation therapy in resectable esophageal squamous cell carcinoma.British journal of cancer · 2025Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found that mutations in NFE2L2, which encodes Nrf2, are associated with a significantly higher rate of LRF in patients with oral cavity cancer treated with surgery and adjuvant (chemo)radiotherapy but not in those treated with surgery alone. Somatic mutation of NFE2L2 led to Nrf2 activation and radioresistance in HNSCC cells. Tumors harboring mutant Nrf2E79Q were substantially more radioresistant than tumors with wild-type Nrf2 in immunocompetent mice, whereas the difference was diminished in immunocompromised mice. Nrf2E79Q enhanced radioresistance through increased recruitment of intratumoral polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and reduction of M1-polarized macrophages. Treatment with the glutaminase inhibitor CB-839 overcame the radioresistance induced by Nrf2E79Q or Nrf2E79K. RT increased expression of PMN-MDSC-attracting chemokines, including CXCL1, CXLC3, and CSF3, in Nrf2E79Q-expressing tumors via the TLR4, which could be reversed by CB-839. This study provides insights into the impact of NFE2L2 mutations on radioresistance and suggests that CB-839 can increase radiosensitivity by switching intratumoral myeloid cells to an antitumor phenotype, supporting clinical testing of CB-839 with RT in HNSCC with NFE2L2 mutations. SIGNIFICANCE: NFE2L2 mutations are predictive biomarkers of radioresistance in head and neck cancer and confer sensitivity to glutaminase inhibitors to overcome radioresistance.
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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.