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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 \u221210.8, \u22129.40, and \u22129.7 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0350614","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:46:23Z","timestamp":1780335983000},"page":"e0350614","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-omics and pan-cancer analysis revealed common molecular signatures to disclose multitargeted anticancer agents through network pharmacology approach"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5394-8777","authenticated-orcid":true,"given":"Hriddhi","family":"Sarker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad 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Data Transformation Using Dplyr Package in R. 2019."},{"key":"pone.0350614.ref052","article-title":"Ggplot2: Elegant Graphics for Data Analysis","volume":"35","author":"PM Valero-Mora","year":"2010","journal-title":"J Stat Softw"},{"key":"pone.0350614.ref053","article-title":"GgVennDiagram: An intuitive, easy-to-use, and highly customizable R package to generate Venn diagram","volume":"12","author":"CH Gao","year":"2021","journal-title":"Frontiers in Genetics"},{"key":"pone.0350614.ref054","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"D Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0350614.ref055","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"key":"pone.0350614.ref056","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","author":"C-H Chin","year":"2014","journal-title":"BMC Syst Biol"},{"key":"pone.0350614.ref057","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx1188","article-title":"JASPAR 2018: Update of the Open-Access Database of Transcription Factor Binding Profiles and Its Web Framework","volume":"46","author":"A Khan","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"pone.0350614.ref058","article-title":"MiRTarBase: A Database Curates Experimentally Validated MicroRNA\u2013Target Interactions","volume":"39","author":"SD Hsu","year":"2011","journal-title":"Nucleic Acids Research"},{"issue":"6","key":"pone.0350614.ref059","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nprot.2015.052","article-title":"NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data","volume":"10","author":"J Xia","year":"2015","journal-title":"Nat Protoc"},{"key":"pone.0350614.ref060","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","author":"BT Sherman","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pone.0350614.ref061","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Z Tang","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pone.0350614.ref062","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","article-title":"UALCAN: An update to the integrated cancer data analysis platform","volume":"25","author":"DS Chandrashekar","year":"2022","journal-title":"Neoplasia"},{"key":"pone.0350614.ref063","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"T Li","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0350614.ref064","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12967-024-05134-6","article-title":"CD8+ T cell-based cancer immunotherapy","volume":"22","author":"Y Chen","year":"2024","journal-title":"J Transl Med"},{"key":"pone.0350614.ref065","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.drudis.2021.01.002","article-title":"Tumor-infiltrating CD8 T cell antitumor efficacy and exhaustion: Molecular insights","volume":"26","author":"S Kumar","year":"2021","journal-title":"Drug Discov Today"},{"key":"pone.0350614.ref066","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"A Bateman","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"pone.0350614.ref067","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaa1038","article-title":"RCSB Protein Data Bank: Powerful New Tools for Exploring 3D Structures of Biological Macromolecules for Basic and Applied Research and Education in Fundamental Biology, Biomedicine, Biotechnology, Bioengineering and Energy Sciences","volume":"49","author":"SK Burley","year":"2021","journal-title":"Nucleic Acids Research"},{"key":"pone.0350614.ref068","unstructured":"BIOVIA, D.S. 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Zigov\u00e1","year":"2024","journal-title":"Molecules"},{"key":"pone.0350614.ref081","doi-asserted-by":"crossref","first-page":"109324","DOI":"10.1016\/j.jmgm.2026.109324","article-title":"Structure-based drug design of sanguinarine derivatives targeting Babesia microti lactate dehydrogenase through computational approaches","volume":"146","author":"MA Ali","year":"2026","journal-title":"J Mol Graph Model"},{"issue":"2","key":"pone.0350614.ref082","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1021\/ci800293n","article-title":"Validation of molecular docking programs for virtual screening against dihydropteroate synthase","volume":"49","author":"KE Hevener","year":"2009","journal-title":"J Chem Inf Model"},{"issue":"3","key":"pone.0350614.ref083","article-title":"Exploring potential phytocompounds from black cumin as drug molecules against SARS-CoV-2 infections through bioinformatics analysis","volume":"21","author":"MA Ali","year":"2026","journal-title":"PLoS 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Khan","year":"2024","journal-title":"Discov Oncol"},{"key":"pone.0350614.ref104","doi-asserted-by":"crossref","first-page":"153936","DOI":"10.1016\/j.prp.2022.153936","article-title":"AURKA is a prognostic biomarker for good overall survival in stage II colorectal cancer patients","volume":"235","author":"P Jung","year":"2022","journal-title":"Pathol Res Pract"},{"key":"pone.0350614.ref105","doi-asserted-by":"crossref","first-page":"40714","DOI":"10.1038\/srep40714","article-title":"Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior","volume":"7","author":"A Mobley","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0350614.ref106","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/jcb.30205","article-title":"The cell cycle\u2010related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients","volume":"123","author":"I Kahl","year":"2022","journal-title":"J Cell 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and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma","volume":"26","author":"Y Zou","year":"2020","journal-title":"Med Sci Monit"},{"key":"pone.0350614.ref111","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s12967-014-0307-x","article-title":"AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues","volume":"12","author":"G Juan","year":"2014","journal-title":"J Transl Med"},{"issue":"23","key":"pone.0350614.ref112","doi-asserted-by":"crossref","first-page":"9846","DOI":"10.1158\/0008-5472.CAN-10-3001","article-title":"Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines","volume":"70","author":"M Payton","year":"2010","journal-title":"Cancer 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