دورية أكاديمية
Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer
| العنوان: | Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer |
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| المؤلفون: | Akiko Takahashi, Masahiro Seike, Mika Chiba, Satoshi Takahashi, Shinji Nakamichi, Masaru Matsumoto, Susumu Takeuchi, Yuji Minegishi, Rintaro Noro, Shinobu Kunugi, Kaoru Kubota, Akihiko Gemma |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018) |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Osimertinib, Afatinib, Ankyrin Repeat Domain (ANKRD1), Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs), EGFR-mutant NSCLC Patients, Medicine, Science |
| الوصف: | Abstract Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is critical in combating EGFR-mutant non-small cell lung cancer (NSCLC). We tried to construct a novel therapeutic strategy to conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive NSCLC patients. We established afatinib- and osimertinib-resistant lung adenocarcinoma cell lines. Exome sequencing, cDNA array and miRNA microarray were performed using the established cell lines to discover novel therapeutic targets associated with the resistance to second-and third-generation EGFR-TKIs. We found that ANKRD1 which is associated with the epithelial-mesenchymal transition (EMT) phenomenon and anti-apoptosis, was overexpressed in the second-and third-generation EGFR-TKIs-resistant cells at the mRNA and protein expression levels. When ANKRD1 was silenced in the EGFR-TKIs-resistant cell lines, afatinib and osimertinib could induce apoptosis of the cell lines. Imatinib could inhibit ANKRD1 expression, resulting in restoration of the sensitivity to afatinib and osimertinib of EGFR-TKI-resistant cells. In EGFR-mutant NSCLC patients, ANKRD1 was overexpressed in the tumor after the failure of EGFR-TKI therapy, especially after long-duration EGFR-TKI treatments. ANKRD1 overexpression which was associated with EMT features and anti-apoptosis, was commonly involved in resistance to second-and third-generation EGFR-TKIs. ANKRD1 inhibition could be a promising therapeutic strategy in EGFR-mutant NSCLC patients. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-018-33190-8 |
| الوصول الحر: | https://doaj.org/article/2d4c5449621342aa816f7c0089346a66Test |
| رقم الانضمام: | edsdoj.2d4c5449621342aa816f7c0089346a66 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-018-33190-8 |