Pyrotinib targeted EGFR/GRP78 mediated cell apoptosis in high EGFR gene copy number gastric cancer.

ABSTRACT:

Background

Despite frequent Epidermal Growth Factor Receptor (EGFR) amplification and overexpression in gastric cancer, limited therapeutic responses were observed in existing EGFR-targeted agents. Pyrotinib, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor, has shown clinical efficacy in HER2-driven malignancies, but its potential role in EGFR-high copy number gastric cancer remains to be investigated.

Methods

Using EGFR-high copy number gastric cancer cell lines, primary cells and subcutaneous tumor models in nude mice, we systematically evaluated pyrotinib's anti-tumor activity through viability assays, apoptosis analysis, and transcriptomic profiling. Mechanistic studies included co-immunoprecipitation, proximity ligation assays, ubiquitination assays, and RNA se

SUBMITTER: Bao L 

PROVIDER: S-EPMC12363034 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature