دورية أكاديمية
Dynamics of multiple resistance mechanisms in plasma DNA during EGFR‐targeted therapies in non‐small cell lung cancer
| العنوان: | Dynamics of multiple resistance mechanisms in plasma DNA during EGFR‐targeted therapies in non‐small cell lung cancer |
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| المؤلفون: | Dana Wai Yi Tsui, Muhammed Murtaza, Alvin Seng Cheong Wong, Oscar M Rueda, Christopher G Smith, Dineika Chandrananda, Ross A Soo, Hong Liang Lim, Boon Cher Goh, Carlos Caldas, Tim Forshew, Davina Gale, Wei Liu, James Morris, Francesco Marass, Tim Eisen, Tan Min Chin, Nitzan Rosenfeld |
| المصدر: | EMBO Molecular Medicine, Vol 10, Iss 6, Pp n/a-n/a (2018) |
| بيانات النشر: | Springer Nature, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | circulating tumour DNA, liquid biopsy, lung cancer, resistance mechanisms, targeted therapy, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Tumour heterogeneity leads to the development of multiple resistance mechanisms during targeted therapies. Identifying the dominant driver(s) is critical for treatment decision. We studied the relative dynamics of multiple oncogenic drivers in longitudinal plasma of 50 EGFR‐mutant non‐small‐cell lung cancer patients receiving gefitinib and hydroxychloroquine. We performed digital PCR and targeted sequencing on samples from all patients and shallow whole‐genome sequencing on samples from three patients who underwent histological transformation to small‐cell lung cancer. In 43 patients with known EGFR mutations from tumour, we identified them accurately in plasma of 41 patients (95%, 41/43). We also found additional mutations, including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%) and PTEN (4/50, 8%). Patients with both TP53 and EGFR mutations before treatment had worse overall survival than those with only EGFR. Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small‐cell lung cancer‐associated copy number changes and TP53 mutations, that tracked subsequent treatment responses. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non‐druggable genetic information that may guide clinical management. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.201707945 |
| URL الوصول: | https://doaj.org/article/359abd7345a3480bbf157d3f3b813302 |
| رقم الأكسشن: | edsdoj.359abd7345a3480bbf157d3f3b813302 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.201707945 |