Multi-omics and pan-cancer analysis revealed common molecular signatures to disclose multitargeted anticancer agents through network pharmacology approach

Abstract

Cancer is characterized as a multifactorial disease due to their complex genetic and molecular mechanisms that often converge across tissue types. Shared oncogenic pathways can help us understand these functions and discover broad-spectrum therapeutics. Earlier, most studies focused on finding specific drivers for individual cancer types. However, researchers are now more interested in identifying common molecular patterns across different cancers and developing therapies that can target multiple pathways at once. This study aimed to understand the common oncogenic pathways between breast, ovarian and colorectal (BOC) cancers and identify possible multitargeted therapeutic drug molecules. To identify the common differentially expressed genes (DEGs), we analyzed three transcriptomic datasets and found a total of 128 DEGs. The protein-protein interaction (PPI) network study reveals the top-ranked, most significant hub targets, AURKA, CDK1 and CCNB1, as drug targets. Enrichment analysis with GO and KEGG pathways, as well as regulatory network (TFs and mRNAs) analysis, revealed common pathogenetic processes among BOC cancers. The AMG-900 exhibits the highest binding affinity scores of −10.8, −9.40, and −9.7 kcal/mol with the target proteins AURKA, CCNB1, and CDK1, respectively. The stability and structural flexibility of the selected protein-ligand complexes were validated by a large-scale (500 ns) molecular dynamics and MM-GBSA analyses, and the results indicate stable interactions for AURKA and CCNB1, while CDK1 showed comparatively reduced stability. The pharmacokinetic analysis revealed favorable drug-likeness and a manageable toxicity profile typical of anticancer agents. Therefore, the findings of this study propose that AMG-900 may serve as a promising multi-targeted candidate for further investigation in multi-target therapeutic strategies within precision oncology. Furthermore, these results require additional experimental (in vivo and in vitro) and clinical validation to confirm the potentiality and efficiency of this (AMG-900) lead compound.