ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2021
Altered Regulation of HIF-1α in Naive- and Drug-Resistant EGFR-Mutant NSCLC: Implications for a Vascular Endothelial Growth Factor-Dependent Phenotype.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Effects of Aidi injection on life quality and incidence of adverse reactions in patients with non-small cell lung cancer compared with traditional chemotherapy: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor-NaïveJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Trial
- RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure-response relationship.Cancer chemotherapy and pharmacology · 2022Trial
- Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.Cancer cell · 2022Trial
- Mitochondrial mechanisms underlying spatial immune phenotypes in non‑small cell lung cancer: Implications for ICI response and cold‑to‑hot tumor conversion (Review).Oncology reports · 2026Review
- The combination of pralsetinib and bevacizumab enhances antitumor activity against KIF5B-RET lung cancer via PI3K/AKT pathway.Journal of thoracic disease · 2026Article
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Prognostic analysis and beneficiary population exploration of subsequent treatment regimens after third-generation EGFR-TKIs failure in EGFR-mutated advanced non-small cell lung cancer: a retrospective cohort study.Translational lung cancer research · 2026Article
- ResMap: A community resource for systematic mapping of therapy-persistent residual cancer cell dependencies across contexts.Science advances · 2026Article
- Red blood cell-derived extracellular vesicles enable cisplatin and cetuximab combined therapy against triple-negative breast cancer.Journal of nanobiotechnology · 2026Article
- Optimal treatment strategies for EGFR mutant advanced lung adenocarcinoma patients with targeted therapy resistance and correlation analysis of PD-L1 expression with ICI efficacy.Scientific reports · 2026Article
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Inhibition of autotaxin sensitizes colon cancer to radiation by suppressing LPAR2-AKT survival signaling.BMC gastroenterology · 2025Article
- Beyond the Scalpel: EGFR Mutation Predicts Intraoperative Blood Loss and Transfusion Needs During Lung Cancer-derived Spinal Metastasis Surgery.Annals of surgical oncology · 2025Article
- Advances in molecular pathology and therapy of non-small cell lung cancer.Signal transduction and targeted therapy · 2025Review
- A Structural Insight Into Two Important ErbB Receptors (EGFR and HER2) and Their Relevance to Non-Small Cell Lung Cancer.Archiv der Pharmazie · 2025Review
- A trispecific antibody targeting EGFR/cMET/VEGF-A demonstrates multiple mechanisms of action to inhibit wild-type and mutant NSCLC animal models.Frontiers in oncology · 2025Article
- PCBP2-dependent secretion of miRNAs via extracellular vesicles contributes to the EGFR-driven angiogenesis.Theranostics · 2025Article
- Risk factors for misclassification in predicting EGFR mutation status using PET/CT imaging in non-small cell lung cancer patients.Frontiers in oncology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionThe treatment of patients with EGFR-mutant NSCLC with vascular endothelial growth factor (VEGF) inhibitors in combination with EGFR inhibitors provides a greater benefit than EGFR inhibition alone, suggesting that EGFR mutation status may define a patient subgroup with greater benefit from VEGF blockade. The mechanisms driving this potentially enhanced VEGF dependence are unknown.
methodsWe analyzed the effect of EGFR inhibition on VEGF and HIF-1α in NSCLC models in vitro and in vivo. We determined the efficacy of VEGF inhibition in xenografts and analyzed the impact of acquired EGFR inhibitor resistance on VEGF and HIF-1α.
resultsNSCLC cells with EGFR-activating mutations exhibited altered regulation of VEGF compared with EGFR wild-type cells. In EGFR-mutant cells, EGFR, not hypoxia, was the dominant regulator of HIF-1α and VEGF. NSCLC tumor models bearing classical or exon 20 EGFR mutations were more sensitive to VEGF inhibition than EGFR wild-type tumors, and a combination of VEGF and EGFR inhibition delayed tumor progression. In models of acquired EGFR inhibitor resistance, whereas VEGF remained overexpressed, the hypoxia-independent expression of HIF-1α was delinked from EGFR signaling, and EGFR inhibition no longer diminished HIF-1α or VEGF expression.
conclusionsIn EGFR-mutant NSCLC, EGFR signaling is the dominant regulator of HIF-1α and VEGF in a hypoxia-independent manner, hijacking an important cellular response regulating tumor aggressiveness. Cells with acquired EGFR inhibitor resistance retained elevated expression of HIF-1α and VEGF, and the pathways were no longer EGFR-regulated. This supports VEGF targeting in EGFR-mutant tumors in the EGFR inhibitor-naive and refractory settings.
Indexed as
Identifiers
What OpenQuestion holds
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.