• TOP2A is significantly overexpressed in adrenocortical carcinoma (ACC) and correlates with poor patient prognosis, establishing it as a promising prognostic biomarker.
• Multi-omics analysis reveals that TOP2A expression levels are associated with distinct gene expression patterns and diminished CD8+ T-cell infiltration, impacting immunotherapy response.
• The study identifies resminostat and etoposide as potential therapeutic inhibitors of TOP2A, with in vivo validation demonstrating their efficacy against ACC tumors.
• These findings provide a foundation for developing targeted therapies and improving clinical management of ACC, addressing the urgent need for novel treatment strategies.