Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma.

Zhuxuan Li,Xueqian Zhuang,Chun-Hao Pan,Yan Yan,Rohit Thummalapalli,Jill Hallin, Stefan Torborg,Anupriya Singhal,Jason C Chang,Eusebio Manchado,Lukas E Dow,Rona Yaeger,James G Christensen,Scott W Lowe,Charles M Rudin,Simon Joost,Tuomas Tammela

bioRxiv : the preprint server for biology（2023）

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摘要

Treatment resistance limits response to KRAS inhibitors in LUAD patients. We find LUAD residual disease following KRAS targeting is composed of AT1-like cancer cells with the capacity to reignite tumorigenesis. Targeting the AT1-like cells augments responses to KRAS inhibition, elucidating a therapeutic strategy to overcome resistance to KRAS-targeted therapy.

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