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

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.