ArticleCancer discovery2017
Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance.
Article in Cancer discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers, 1 of them a synthesis that pooled it.
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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
216 citing papers in PubMed, 1 synthesis or guideline pooled it, 357 citations in OpenAlex.
- Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis.PloS one · 2020Pooled it
- Preoperative chemoradiotherapy plus pembrolizumab for esophageal squamous cell carcinoma (ACTS-29).Esophagus : official journal of the Japan Esophageal Society · 2026Trial
- 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
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.Nature communications · 2026Article
- Injectable Microenvironment-Responsive Hydrogel for Local Procyanidin B2 Delivery and Cardiac Ischemia-Reperfusion Repair.ACS applied materials & interfaces · 2026Article
- A chronic whole cigarette smoke extract model reveals redox-mitochondrial adaptation in human lung epithelial and organoid models.Experimental & molecular medicine · 2026Article
- A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth.Cancer discovery · 2026Article
- Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.Biomolecules · 2026Review
- Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition.Frontiers in cell and developmental biology · 2026Review
- TheCancer management and research · 2026Review
- Mitochondrial metabolic-transcriptional axis drives adaptive drug tolerance across major lung cancer subtypes.Frontiers in genetics · 2026Review
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- TMPRSS11B promotes an acidified microenvironment and immune suppression in squamous lung cancer.EMBO reports · 2025Article
- Impact of RAS-MAPK Pathway Genetic Alterations on Radiotherapy Response in Metastatic Lung Adenocarcinoma.JCO precision oncology · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- FAM83A is a prognostic biomarker for lung squamous cell carcinoma and correlated with immunoregulation.Scientific reports · 2025Article
- Resistance to radiation enhances metastasis by altering RNA metabolism.Science advances · 2025Article
156 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
Lung squamous cell carcinoma (LSCC) pathogenesis remains incompletely understood, and biomarkers predicting treatment response remain lacking. Here, we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histologic and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in patients with non-small lung cancer (NSCLC) and could be noninvasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. SIGNIFICANCE: We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86-101. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.
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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.