Targeting AURKB Attenuates Tumor Growth in MYC-driven Lung Adenocarcinoma

Aurora kinase B (AURKB) is a key mitotic regulator frequently overexpressed in various malignancies. However, its functional link and therapeutic relevance in MYC-driven lung adenocarcinoma (LUAD) have not been fully elucidated. This study aimed to investigate whether targeting AURKB could attenuate tumor growth by disrupting MYC-mediated oncogenic programs in LUAD.

AURKB expression and its clinical significance were analyzed using public cancer datasets. Molecular crosstalk between AURKB and MYC signaling was evaluated via Gene Set Enrichment Analysis (GSEA). In vitro, the effects of AURKB inhibition (siRNA or AZD2811) on MYC target genes were assessed by RT-qPCR. Finally, the synergistic antitumor effect of dual AURKB (AZD2811) and MYC (MYCi361) inhibition was validated in an H1299 xenograft mouse model.

High AURKB expression was associated with poor overall survival in LUAD patients and significantly correlated with the enrichment of MYC target signatures. Genetic or pharmacological inhibition of AURKB led to a significant reduction in the mRNA expression of core MYC target genes (CDC20, CCNA2, and CDC45), which themselves were identified as independent poor prognostic factors. In the xenograft model, combined treatment with AZD2811 and MYCi361 resulted in a superior reduction in tumor volume and weight compared to either monotherapy.

AURKB contributes to LUAD progression by modulating MYC-driven oncogenic programs. Consequently, targeting the AURKB/MYC axis may represent a potential therapeutic strategy for MYC-dependent lung adenocarcinoma.