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Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking

G724S is a rare mutation induced by different generations of tyrosine kinase inhibitors (TKIs). No clinical effective drugs toward G724S mutation have been reported till now. We analyzed the interaction of three drugs (afatinib, gefitinib, osimertinib) with epidermal growth factor receptor (EGFR) fr...

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Autores principales: Yu, Nian, Xu, Yinghui, Wang, Xu, Sun, Chao, Qiu, Shi, Guo, Ye, Bai, Miao, Huang, Yanxin, Ma, Kewei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571774/
https://www.ncbi.nlm.nih.gov/pubmed/34396638
http://dx.doi.org/10.1002/onco.13932
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author Yu, Nian
Xu, Yinghui
Wang, Xu
Sun, Chao
Qiu, Shi
Guo, Ye
Bai, Miao
Huang, Yanxin
Ma, Kewei
author_facet Yu, Nian
Xu, Yinghui
Wang, Xu
Sun, Chao
Qiu, Shi
Guo, Ye
Bai, Miao
Huang, Yanxin
Ma, Kewei
author_sort Yu, Nian
collection PubMed
description G724S is a rare mutation induced by different generations of tyrosine kinase inhibitors (TKIs). No clinical effective drugs toward G724S mutation have been reported till now. We analyzed the interaction of three drugs (afatinib, gefitinib, osimertinib) with epidermal growth factor receptor (EGFR) from three aspects: the spatial structure of the binding region, the scoring function value, and the interaction force between drug molecules and active center of EGFR. Our results indicate that afatinib remains effective to patients with EGFR Exon19Deletion(Ex19Del) and G724S mutations whereas osimertinib and gefitinib are not, which is consistent with other reports. Afatinib is reported to be effective against G724S mutation, but no long‐term clinical survival has been reported till now. A patient with stage IV adenocarcinoma was found to have Ex19Del/G724S mutation. Treated with afatinib, he received a progression‐free survival of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using afatinib for patients with G724S mutations and obtaining long‐term clinical survival. KEY POINTS: Guided by protein‐drug docking, afatinib is more effective to EGFR G724S mutation compared with osimertinib and gefitinib. A patient with Ex19Del/G724S mutation obtained long‐term survival with afatinib treatment.
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spelling pubmed-85717742021-11-10 Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking Yu, Nian Xu, Yinghui Wang, Xu Sun, Chao Qiu, Shi Guo, Ye Bai, Miao Huang, Yanxin Ma, Kewei Oncologist Precision Medicine Clinic: Molecular Tumor Board G724S is a rare mutation induced by different generations of tyrosine kinase inhibitors (TKIs). No clinical effective drugs toward G724S mutation have been reported till now. We analyzed the interaction of three drugs (afatinib, gefitinib, osimertinib) with epidermal growth factor receptor (EGFR) from three aspects: the spatial structure of the binding region, the scoring function value, and the interaction force between drug molecules and active center of EGFR. Our results indicate that afatinib remains effective to patients with EGFR Exon19Deletion(Ex19Del) and G724S mutations whereas osimertinib and gefitinib are not, which is consistent with other reports. Afatinib is reported to be effective against G724S mutation, but no long‐term clinical survival has been reported till now. A patient with stage IV adenocarcinoma was found to have Ex19Del/G724S mutation. Treated with afatinib, he received a progression‐free survival of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using afatinib for patients with G724S mutations and obtaining long‐term clinical survival. KEY POINTS: Guided by protein‐drug docking, afatinib is more effective to EGFR G724S mutation compared with osimertinib and gefitinib. A patient with Ex19Del/G724S mutation obtained long‐term survival with afatinib treatment. John Wiley & Sons, Inc. 2021-09-12 2021-11 /pmc/articles/PMC8571774/ /pubmed/34396638 http://dx.doi.org/10.1002/onco.13932 Text en © 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Precision Medicine Clinic: Molecular Tumor Board
Yu, Nian
Xu, Yinghui
Wang, Xu
Sun, Chao
Qiu, Shi
Guo, Ye
Bai, Miao
Huang, Yanxin
Ma, Kewei
Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title_full Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title_fullStr Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title_full_unstemmed Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title_short Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein‐Drug Docking
title_sort successful treatment of afatinib reversing epidermal growth factor receptor exon19deletion/g724s mutation resistance guided by protein‐drug docking
topic Precision Medicine Clinic: Molecular Tumor Board
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571774/
https://www.ncbi.nlm.nih.gov/pubmed/34396638
http://dx.doi.org/10.1002/onco.13932
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