Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures.

ABSTRACT: Osimertinib is the first-line therapy for EGFR-mutated non-small cell lung cancer, but acquired resistance emerges in most patients and remains a major barrier for complete cure. This phenomenon is most likely associated with the drug-tolerant persister (DTP) cell phenotype, a reversible state that enables survival under treatment and leads to irreversible drug resistance. To uncover the molecular mechanism driving this distinct phenotype, we applied data-independent acquisition mass spectrometry (DIA-MS) to establish the dynamic proteomic and phosphoproteomic landscape in the osimertinib DTPs. While osimertinib initially blocks EGFR signaling, ribosome synthesis and protein translation related pathways arise in DTP phase, and resistance developed through the reactivation of EGFR downstrea

SUBMITTER: Hsu HE 

PROVIDER: S-EPMC12583488 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature