LAUSR

NCI‐60 growth inhibition and gene expression profiles were analyzed using Pearson correlation and functional enrichment computational tools to demonstrate critical mechanistic differences between a nucleolus‐targeting platinum‐acridine anticancer agent (PA) and other DNA‐directed chemotherapies. The results support prior experimental data and are consistent with DNA being a major target of the hybrid agent based on the negative correlations observed between its potency and expression levels of genes implicated in DNA double‐strand break (DSB) repair. Gene ontology terms related to RNA processing, including ribosome biogenesis, are also negatively enriched, suggesting a mechanism by which these processes render cancer cells more resistant to the highly cytotoxic agent. The opposite trend is observed for oxaliplatin and other DNA‐targeted drugs. Significant functional interactions exist between genes/gene products involved in ribosome biogenesis and DSB repair, including the ribosomal protein (RPL5)‐MDM2‐p53 surveillance pathway, as a response to the nucleolar stress produced by PAs.