Academic Journal
Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer
| العنوان: | Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer |
|---|---|
| المؤلفون: | Chike Osude, Leo Lin, Meet Patel, Adam Eckburg, Joseph Berei, Adijan Kuckovic, Namrata Dube, Aayush Rastogi, Shruti Gautam, Thomas J. Smith, Shylendra B. Sreenivassappa, Neelu Puri |
| المصدر: | Cells, Vol 11, Iss 10, p 1694 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | non-small cell lung cancer (NSCLC), tyrosine kinase inhibitor (TKI), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor (VEGF), neuropilin-1 (NP-1), Cytology, QH573-671 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2073-4409 |
| Relation: | https://www.mdpi.com/2073-4409/11/10/1694; https://doaj.org/toc/2073-4409 |
| DOI: | 10.3390/cells11101694 |
| URL الوصول: | https://doaj.org/article/aa83e90141d14f91a0783e80526c33ad |
| رقم الانضمام: | edsdoj.83e90141d14f91a0783e80526c33ad |
| قاعدة البيانات: | Directory of Open Access Journals |
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