What question did this study set out to answer?

To characterize the genomic and phenotypic mechanisms causing acquired resistance to osimertinib in patients with EGFR T790M-positive lung adenocarcinoma.

September 3, 2026Frontiers in GeneticsOpen Access

Mechanisms of acquired resistance to osimertinib in EGFR T790M-Positive lung adenocarcinoma

View Full Paper

Ask AI

Bookmark

Authors

KCKefan Cui RZRenjie Zhu JLJingmeng LiQujiang People's Hospital

Discussion

Member takes

Implication

Retrospective study uncovers diverse genomic and histological resistance mechanisms to osimertinib in EGFR T790M lung adenocarcinoma, highlighting targets for tailored subsequent therapies.

Key Points

To characterize the genomic and phenotypic mechanisms causing acquired resistance to osimertinib in patients with EGFR T790M-positive lung adenocarcinoma.
Retrospectively analyzed clinical records of 86 patients with EGFR T790M lung adenocarcinoma who developed disease progression on osimertinib between January 2018 and December 2023.
Identified resistance alterations via next-generation sequencing of post-resistance tissue or liquid biopsies, evaluated protein expression with immunohistochemistry, and validated pathways in cell lines.
Median time to disease progression was 14.2 months, driven by primary resistance alterations including EGFR C797S (23.3%), MET amplification (15.1%), epithelial-mesenchymal transition (12.8%), small cell lung cancer transformation (9.3%), HER2 amplification (8.1%), and PIK3CA mutations (7.0%).
Multiple concurrent resistance mechanisms occurred in 24.4% of patients, while C797S mutations appeared in cis (65.0%), trans (30.0%), or mixed (5.0%) configurations with T790M.
Histological transformation was linked to the poorest clinical outcome, resulting in a median overall survival of 8.3 months following confirmed disease progression.

Cite This Study

Cui et al. (2026) studied this question.

synapsesocial.com/papers/6aaa1331207060c46bfbc0e3 https://doi.org/10.3389/fgene.2026.1827187

View Full Paper

Ask AI

Bookmark

Implication

Retrospective study uncovers diverse genomic and histological resistance mechanisms to osimertinib in EGFR T790M lung adenocarcinoma, highlighting targets for tailored subsequent therapies.

Mechanisms of acquired resistance to osimertinib in EGFR T790M-Positive lung adenocarcinoma

Discussion

Member takes

Implication

Key Points

Cite This Study

Mechanisms of acquired resistance to osimertinib in EGFR T790M-Positive lung adenocarcinoma

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider