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Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

Ionizing radiation (IR) is the central component of the therapeutic scheme for nasopharyngeal carcinoma (NPC) at present. Previous studies show that inhibition of epidermal growth factor receptor (EGFR) enhances the radiosensitivity of NPC; however the effects of EGFR-targeted agents are limited. In...

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Autores principales: Huang, Fangling, Liang, Xujun, Min, Xiaoli, Zhang, Ye, Wang, Guoqiang, Peng, Zhengrong, Peng, Fang, Li, Maoyu, Chen, Lin, Chen, Yongheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548161/
https://www.ncbi.nlm.nih.gov/pubmed/31205567
http://dx.doi.org/10.7150/jca.29327
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author Huang, Fangling
Liang, Xujun
Min, Xiaoli
Zhang, Ye
Wang, Guoqiang
Peng, Zhengrong
Peng, Fang
Li, Maoyu
Chen, Lin
Chen, Yongheng
author_facet Huang, Fangling
Liang, Xujun
Min, Xiaoli
Zhang, Ye
Wang, Guoqiang
Peng, Zhengrong
Peng, Fang
Li, Maoyu
Chen, Lin
Chen, Yongheng
author_sort Huang, Fangling
collection PubMed
description Ionizing radiation (IR) is the central component of the therapeutic scheme for nasopharyngeal carcinoma (NPC) at present. Previous studies show that inhibition of epidermal growth factor receptor (EGFR) enhances the radiosensitivity of NPC; however the effects of EGFR-targeted agents are limited. In this study, we observed that simultaneously inhibition of EGFR and HER2 by afatinib could augment the radiosensitivity of NPC cells; this approach has an advantage over erlotinib-mediated inhibition of EGFR alone. The afatinib-induced augmentation of NPC cell radiosensitivity was associated with increases in apoptosis and accumulation of DNA damage that were induced by radiation. In addition, the crosstalk between radiation-induced activities and EGFR-, and HER2-related downstream pathways may contribute to the enhancement of radiosensitivity. Our findings indicate the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells.
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spelling pubmed-65481612019-06-14 Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells Huang, Fangling Liang, Xujun Min, Xiaoli Zhang, Ye Wang, Guoqiang Peng, Zhengrong Peng, Fang Li, Maoyu Chen, Lin Chen, Yongheng J Cancer Research Paper Ionizing radiation (IR) is the central component of the therapeutic scheme for nasopharyngeal carcinoma (NPC) at present. Previous studies show that inhibition of epidermal growth factor receptor (EGFR) enhances the radiosensitivity of NPC; however the effects of EGFR-targeted agents are limited. In this study, we observed that simultaneously inhibition of EGFR and HER2 by afatinib could augment the radiosensitivity of NPC cells; this approach has an advantage over erlotinib-mediated inhibition of EGFR alone. The afatinib-induced augmentation of NPC cell radiosensitivity was associated with increases in apoptosis and accumulation of DNA damage that were induced by radiation. In addition, the crosstalk between radiation-induced activities and EGFR-, and HER2-related downstream pathways may contribute to the enhancement of radiosensitivity. Our findings indicate the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. Ivyspring International Publisher 2019-05-12 /pmc/articles/PMC6548161/ /pubmed/31205567 http://dx.doi.org/10.7150/jca.29327 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Huang, Fangling
Liang, Xujun
Min, Xiaoli
Zhang, Ye
Wang, Guoqiang
Peng, Zhengrong
Peng, Fang
Li, Maoyu
Chen, Lin
Chen, Yongheng
Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title_full Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title_fullStr Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title_full_unstemmed Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title_short Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
title_sort simultaneous inhibition of egfr and her2 via afatinib augments the radiosensitivity of nasopharyngeal carcinoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548161/
https://www.ncbi.nlm.nih.gov/pubmed/31205567
http://dx.doi.org/10.7150/jca.29327
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