ArticleCells2022
Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Efficacy and Tolerability of Ramucirumab Plus Erlotinib in Taiwanese Patients with Untreated, Epidermal Growth Factor Receptor-Mutated, Stage IV Non-small Cell Lung Cancer in the RELAY Study.Targeted oncology · 2023Trial
- HIF-1α siRNA Enhances the Efficacy of Erlotinib in Non-small Cell Lung Cancer: A Novel Strategy to Reverse Hypoxia-Induced Drug Resistance.Drugs in R&D · 2026Article
- Evaluation of gefitinib alone or combined with bevacizumab in patients withTranslational lung cancer research · 2025Article
- The Role of Fat Mass and Obesity-Associated (FTO) Gene in Non-Small Cell Lung Cancer Tumorigenicity and EGFR Tyrosine Kinase Inhibitor Resistance.Biomedicines · 2025Article
- Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges.Biomedicines · 2025Review
- Durvalumab, Tremelimumab, and Platinum Chemotherapy inJTO clinical and research reports · 2025Article
- Addition of bevacizumab to gefitinib plus chemotherapy as first-line therapy in EGFR L858R mutate advanced non-small cell lung cancer patients.Frontiers in pharmacology · 2025Article
- Review
- Clinical efficacy of Apatinib combined with Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer after EGFR-TKI resistance.Pakistan journal of medical sciences · 2024Article
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- Clinicopathological impact of VEGFR2 and VEGF-C in patients with EGFR-major mutant NSCLC receiving osimertinib.Thoracic cancer · 2023Article
- Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma.Cancer medicine · 2023Article
- Low‑dose anlotinib combined with EGFR‑TKI can be used as an alternative for EGFR‑TKI‑resistant non‑small cell lung cancer in elderly patients.Oncology letters · 2023Article
- Article
- Article
- Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment.Frontiers in pharmacology · 2023Review
- Treatment decision-making for leptomeningeal metastasis after TKI resistance in EGFR-mutant lung cancer: a comprehensive review on staging, resistance patterns, and multimodal interventions.Frontiers in neurologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NSCLC treatment includes targeting of EGFR with tyrosine kinase inhibitors (TKIs) such as Erlotinib; however, resistance to TKIs is commonly acquired through T790M EGFR mutations or overexpression of vascular endothelial growth factor receptor-2 (VEGFR-2). We investigated the mechanisms of EGFR-TKI resistance in NSCLC cell lines with EGFR mutations or acquired resistance to Erlotinib. These studies showed upregulated gene and protein expression of VEGF, VEGFR-2, and a VEGF co-receptor neuropilin-1 (NP-1) in Erlotinib-resistant (1.4-5.3-fold) and EGFR double-mutant (L858R and T790M; 4.1-8.3-fold) NSCLC cells compared to parental and EGFR single-mutant (L858R) NSCLC cell lines, respectively. Immunofluorescence and FACS analysis revealed increased expression of VEGFR-2 and NP-1 in EGFR-TKI-resistant cell lines compared to TKI-sensitive cell lines. Cell proliferation assays showed that treatment with a VEGFR-2 inhibitor combined with Erlotinib lowered cell survival in EGFR double-mutant NSCLC cells to 9% compared to 72% after treatment with Erlotinib alone. Furthermore, Kaplan-Meier analysis revealed shorter median survival in late-stage NSCLC patients with high vs. low VEGFR-2 expression (14 mos vs. 21 mos). The results indicate that VEGFR-2 may play a key role in EGFR-TKI resistance and that combined treatment of Erlotinib with a VEGFR-2 inhibitor may serve as an effective therapy in NSCLC patients with EGFR mutations.
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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.