{"doi":"10.1038/s42003-025-08699-0","title":"3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer","abstract":"Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact EMT-related morphological changes are understudied, due to the complete failure of typical live/dead 2D high-throughput screens to capture morphology or the lack of robustness of 3D screens. We designed a high-throughput screen using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies. One of these drugs, azithromycin, increased colony circularity, enhanced E-cadherin membrane localization and ZO-1 localization to tight junctions, caused transcriptomic changes consistent with downregulation of EMT, and elevated sensitivity to the chemotherapeutic, irinotecan. A retrospective analysis of patient data demonstrated that the use of azithromycin in patients undergoing treatment for CRC with irinotecan had improved the 5 year survival compared to the chemotherapy alone. These results highlight the importance of morphological screens to identify novel drug candidates and synergistic mechanisms.","journal":"Communications Biology","year":2025,"id":526616,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"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":1311607,"name":"Thomas P. Hasaka","orcid":null,"position":1,"is_corresponding":false},{"id":793166,"name":"Chelsie K. Sievers","orcid":"0000-0003-0088-753X","position":2,"is_corresponding":false},{"id":1400138,"name":"Seung Woo Kang","orcid":"0009-0003-4328-5683","position":3,"is_corresponding":false},{"id":619368,"name":"Marisol Ramirez","orcid":null,"position":4,"is_corresponding":false},{"id":1236508,"name":"Vivian Truong Jones","orcid":null,"position":5,"is_corresponding":false},{"id":361424,"name":"Zhiguo Zhao","orcid":"0000-0002-9033-7410","position":6,"is_corresponding":false},{"id":769583,"name":"Oleg Kovtun","orcid":"0000-0001-6809-9332","position":7,"is_corresponding":false},{"id":1169607,"name":"Claudia C. Wahoski","orcid":null,"position":8,"is_corresponding":false},{"id":430244,"name":"Qi Liu","orcid":"0000-0002-5684-7396","position":9,"is_corresponding":false},{"id":60556,"name":"Ken S. Lau","orcid":"0000-0001-8438-0319","position":10,"is_corresponding":false},{"id":86857,"name":"Robert J. Coffey","orcid":"0000-0002-2180-3844","position":11,"is_corresponding":false},{"id":298993,"name":"Joshua A. Bauer","orcid":"0000-0002-8019-900X","position":12,"is_corresponding":false},{"id":795083,"name":"Bhuminder Singh","orcid":"0000-0003-1357-2158","position":13,"is_corresponding":false},{"id":393388,"name":"Sarah Harmych","orcid":"0000-0001-9967-5398","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40847193","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":[]}