Structure-based classification predicts drug response in EGFR-mutant NSCLC
© 2021. The Author(s)..
Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC)1-3. Targeted therapies are approved for patients with 'classical' mutations and a small number of other mutations4-6. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown1,3,7-10. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure-function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure-function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations.
| Errataetall: |
CommentIn: Cancer Cell. 2021 Nov 8;39(11):1455-1457. - PMID 34752753 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:597 |
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| Enthalten in: |
Nature - 597(2021), 7878 vom: 15. Sept., Seite 732-737 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Robichaux, Jacqulyne P [VerfasserIn] |
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| Links: |
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| Themen: |
41UD74L59M |
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| Anmerkungen: |
Date Completed 07.02.2022 Date Revised 27.07.2022 published: Print-Electronic CommentIn: Cancer Cell. 2021 Nov 8;39(11):1455-1457. - PMID 34752753 Citation Status MEDLINE |
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| doi: |
10.1038/s41586-021-03898-1 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330687093 |
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| 245 | 1 | 0 | |a Structure-based classification predicts drug response in EGFR-mutant NSCLC |
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| 500 | |a CommentIn: Cancer Cell. 2021 Nov 8;39(11):1455-1457. - PMID 34752753 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC)1-3. Targeted therapies are approved for patients with 'classical' mutations and a small number of other mutations4-6. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown1,3,7-10. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure-function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure-function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Lin, Heather Y |e verfasserin |4 aut | |
| 700 | 1 | |a Udagawa, Hibiki |e verfasserin |4 aut | |
| 700 | 1 | |a Skoulidis, Ferdinandos |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Varghese, Susan |e verfasserin |4 aut | |
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