{"doi":"10.1093/emph/eoaf021","title":"Dual targeting of conserved cell cycle and transcription programs in advanced colorectal cancer by fadraciclib","abstract":"Background and objectives: Control of cell division is tightly regulated in eukaryotic cells, and dysfunction in cell cycle checkpoints is a key hallmark of malignant transformation that promotes a fitness advantage over non-cancer cells. One of the most critical mechanisms of cell cycle regulation is via the cyclin-dependent kinases (CDKs), which connect resource availability sensing and growth signaling with cell division and transcription elongation processes. Novel combination therapy approaches to co-target cell cycle and transcriptional CDKs may improve cancer-specific targeting of CDK dysfunction. In the current study, we assessed the effectiveness of fadraciclib, a new CDK2/9 inhibitor, for the treatment of advanced colorectal cancer (CRC). Methodology: A panel of eighteen CRC patient-derived organoids (PDOs) was used to assess the efficacy of fadraciclib. Efficacy was further validated in patient-derived xenografts (PDXs). CDK2/9 target inhibition, cell cycle arrest, and cell killing mechanisms were investigated using western blotting, flow cytometry, and immunofluorescence staining, respectively. Results: < .05) and no serious adverse effects. Fadraciclib induced G2/M cell cycle arrest, leading to multipolar mitosis and anaphase catastrophe. Conclusions and implications: Our results using patient-derived models suggest that fadraciclib is a promising therapy for advanced CRC by inhibiting CDKs 2 and 9, which affects critical pathways in cell cycle regulation and transcription.","journal":"Evolution Medicine and Public Health","year":2025,"id":572116,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9671,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1122302,"name":"Wylie K. Watlington","orcid":"0009-0004-5335-6518","position":1,"is_corresponding":false},{"id":1122301,"name":"Divya L. Dayanidhi","orcid":"0009-0000-3610-167X","position":2,"is_corresponding":false},{"id":339318,"name":"John B. Mantyh","orcid":"0009-0006-7431-7985","position":3,"is_corresponding":false},{"id":339316,"name":"Gabrielle Rupprecht","orcid":"0000-0003-3711-862X","position":4,"is_corresponding":false},{"id":70187,"name":"Shannon J. McCall","orcid":"0000-0003-3957-061X","position":5,"is_corresponding":false},{"id":1478365,"name":"David Blake","orcid":"0000-0002-8367-3256","position":6,"is_corresponding":false},{"id":339312,"name":"Jason A. Somarelli","orcid":"0000-0003-1510-9343","position":7,"is_corresponding":false},{"id":239529,"name":"David S. Hsu","orcid":"0000-0002-8149-7180","position":8,"is_corresponding":false},{"id":1406275,"name":"Mohammad Zokaasadi","orcid":"0000-0001-8957-0541","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:57:23.653298Z","pmid":"41069959","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}