Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

A recent clinical trial shows that a proportion of lung cancer patients carrying the EGFR T790M mutation develop resistance to osimertinib. In this study, the authors show that T790M subclonality is associated with worse clinical outcome likely through co-occurring PIK3CA alterations, which can be t...

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Main Authors:	Tereza Vaclova, Ursula Grazini, Lewis Ward, Daniel O’Neill, Aleksandra Markovets, Xiangning Huang, Juliann Chmielecki, Ryan Hartmaier, Kenneth S. Thress, Paul D. Smith, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-03-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-021-22057-8

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spelling	doaj-481ad63fcd374f3eb7bb421d24c7891e2021-03-21T12:13:31ZengNature Publishing GroupNature Communications2041-17232021-03-0112111110.1038/s41467-021-22057-8Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancersTereza Vaclova0Ursula Grazini1Lewis Ward2Daniel O’Neill3Aleksandra Markovets4Xiangning Huang5Juliann Chmielecki6Ryan Hartmaier7Kenneth S. Thress8Paul D. Smith9J. Carl Barrett10Julian Downward11Elza C. de Bruin12Translational Medicine, Oncology R&D, AstraZenecaBioscience, Oncology R&D, AstraZenecaDiscovery Science, BioPharmaceutical R&D, AstraZenecaDiscovery Science, BioPharmaceutical R&D, AstraZenecaTranslational Medicine, Oncology R&D, AstraZenecaBiometrics Oncology, Oncology R&D, AstraZenecaTranslational Medicine, Oncology R&D, AstraZenecaTranslational Medicine, Oncology R&D, AstraZenecaTranslational Medicine, Oncology R&D, AstraZenecaBioscience, Oncology R&D, AstraZenecaTranslational Medicine, Oncology R&D, AstraZenecaOncogene Biology, Francis Crick InstituteTranslational Medicine, Oncology R&D, AstraZenecaA recent clinical trial shows that a proportion of lung cancer patients carrying the EGFR T790M mutation develop resistance to osimertinib. In this study, the authors show that T790M subclonality is associated with worse clinical outcome likely through co-occurring PIK3CA alterations, which can be targeted by PI3K pathway inhibitors.https://doi.org/10.1038/s41467-021-22057-8
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Tereza Vaclova Ursula Grazini Lewis Ward Daniel O’Neill Aleksandra Markovets Xiangning Huang Juliann Chmielecki Ryan Hartmaier Kenneth S. Thress Paul D. Smith J. Carl Barrett Julian Downward Elza C. de Bruin
spellingShingle	Tereza Vaclova Ursula Grazini Lewis Ward Daniel O’Neill Aleksandra Markovets Xiangning Huang Juliann Chmielecki Ryan Hartmaier Kenneth S. Thress Paul D. Smith J. Carl Barrett Julian Downward Elza C. de Bruin Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers Nature Communications
author_facet	Tereza Vaclova Ursula Grazini Lewis Ward Daniel O’Neill Aleksandra Markovets Xiangning Huang Juliann Chmielecki Ryan Hartmaier Kenneth S. Thress Paul D. Smith J. Carl Barrett Julian Downward Elza C. de Bruin
author_sort	Tereza Vaclova
title	Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
title_short	Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
title_full	Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
title_fullStr	Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
title_full_unstemmed	Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
title_sort	clinical impact of subclonal egfr t790m mutations in advanced-stage egfr-mutant non-small-cell lung cancers
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2021-03-01
description	A recent clinical trial shows that a proportion of lung cancer patients carrying the EGFR T790M mutation develop resistance to osimertinib. In this study, the authors show that T790M subclonality is associated with worse clinical outcome likely through co-occurring PIK3CA alterations, which can be targeted by PI3K pathway inhibitors.
url	https://doi.org/10.1038/s41467-021-22057-8
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Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

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