The Potential Therapeutic Regimen for Overcoming Resistance to Osimertinib Due to Rare Mutations in NSCLC

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jul 7

PMID 37416479

Authors

Rui Han

Caiyu Lin

Chong Zhang

Jun Kang

Conghua Lu

Yiming Zhang

Yubo Wang

Chen Hu

Yong He

Affiliations

Soon will be listed here.

Abstract

The mechanisms of osimertinib resistance have not been well characterized. We conducted next-generation sequencing to recognize novel resistance mechanism and used cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models to evaluate the anti-proliferative effects of aspirin and . We observed that mutations led to acquired resistance to osimertinib in a patient and further confirmed that both and mutations caused osimertinib resistance. Mechanistically, the expression of PI3Kγ or PI3Kα was up-regulated after or lentivirus transfection, respectively, and which can be effectively suppressed by aspirin. Lastly, our results from studies indicate that aspirin can reverse osimertinib resistance caused by or mutations in both CDX and PDX models. Herein, we first confirmed that mutations in can lead to resistance to osimertinib, and the combined therapy may be a strategy to reverse / mutation-induced osimertinib resistance.

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