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Overcoming MET-targeted drug resistance in MET-amplified lung cancer by Aurora Kinase B inhibition

ABSTRACT: This study investigates the mechanisms of resistance to MET-targeted therapy in MET-amplified lung cancer. Researchers established a lung cancer cell line resistant to MET tyrosine kinase inhibitors (MET-TKI) and found that Aurora kinase B (AURKB) inhibitors significantly inhibited the proliferation of these resistant cells. AURKB knockdown enhanced MET-TKI sensitivity, though the phosphorylation of Histone H3, an AURKB target, remained unchanged. Gene expression analysis revealed an enrichment of STAT3-activated genes, and AURKB influenced the phosphorylation of STAT3. The study also identified an elevated expression of the anti-apoptotic gene BCL2, and AURKB inhibition induced apoptosis by reducing the STAT3/BCL2 axis. The effects of AURKB inhibitors led to G2/M cell cycle arrest and apoptosis in resistant cells. AURKB overexpression was observed in post-treatment tumors from advanced MET-amplified lung cancer patients with MET-TKI resistance. This suggests that targeting AURKB may be a potential therapeutic strategy to overcome resistance to MET-TKIs in MET-amplified lung cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285996 | GEO | 2026/06/30

REPOSITORIES: GEO

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