{"doi":"10.1093/toxsci/kfae041","title":"Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs—a proof-of-concept study with doxorubicin","abstract":"Many oncology drugs have been found to induce cardiotoxicity in a subset of patients, which significantly limits their clinical use and impedes the benefit of lifesaving anticancer treatments. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carry donor-specific genetic information and have been proposed for exploring the interindividual difference in oncology drug-induced cardiotoxicity. Herein, we evaluated the inter- and intraindividual variability of iPSC-CM-related assays and presented a proof of concept to prospectively predict doxorubicin (DOX)-induced cardiotoxicity (DIC) using donor-specific iPSC-CMs. Our findings demonstrated that donor-specific iPSC-CMs exhibited greater line-to-line variability than the intraindividual variability in impedance cytotoxicity and transcriptome assays. The variable and dose-dependent cytotoxic responses of iPSC-CMs resembled those observed in clinical practice and largely replicated the reported mechanisms. By categorizing iPSC-CMs into resistant and sensitive cell lines based on their time- and concentration-related phenotypic responses to DOX, we found that the sensitivity of donor-specific iPSC-CMs to DOX may predict in vivo DIC risk. Furthermore, we identified a differentially expressed gene, DND microRNA-mediated repression inhibitor 1 (DND1), between the DOX-resistant and DOX-sensitive iPSC-CMs. Our results support the utilization of donor-specific iPSC-CMs in assessing interindividual differences in DIC. Further studies will encompass a large panel of donor-specific iPSC-CMs to identify potential novel molecular and genetic biomarkers for predicting DOX and other oncology drug-induced cardiotoxicity.","journal":"Toxicological Sciences","year":2024,"id":465163,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1296272,"name":"Chengzhong Cai","orcid":"0000-0002-0151-5220","position":1,"is_corresponding":false},{"id":751576,"name":"Praful Aggarwal","orcid":null,"position":2,"is_corresponding":false},{"id":655700,"name":"Dong Wang","orcid":"0000-0001-9103-5994","position":3,"is_corresponding":false},{"id":638679,"name":"Vikrant Vijay","orcid":"0000-0001-8425-1285","position":4,"is_corresponding":false},{"id":912460,"name":"Prathyusha Bagam","orcid":"0000-0002-8186-4059","position":5,"is_corresponding":false},{"id":1245775,"name":"Jacob Blamer","orcid":null,"position":6,"is_corresponding":false},{"id":764508,"name":"Andrea Matter","orcid":"0000-0002-7117-8987","position":7,"is_corresponding":false},{"id":728885,"name":"Amy Turner","orcid":"0000-0003-0867-7545","position":8,"is_corresponding":false},{"id":1296273,"name":"Lijun Ren","orcid":"0000-0001-5957-1113","position":9,"is_corresponding":false},{"id":1296652,"name":"Katy S Papineau","orcid":null,"position":10,"is_corresponding":false},{"id":708126,"name":"Vinodh Srinivasasainagendra","orcid":null,"position":11,"is_corresponding":false},{"id":25027,"name":"Hemant K. Tiwari","orcid":null,"position":12,"is_corresponding":false},{"id":1296274,"name":"Xi Yang","orcid":"0000-0002-3427-0565","position":13,"is_corresponding":false},{"id":694309,"name":"Laura K. Schnackenberg","orcid":null,"position":14,"is_corresponding":false},{"id":12934,"name":"William B. Mattes","orcid":"0000-0001-8653-4289","position":15,"is_corresponding":false},{"id":24701,"name":"Ulrich Broeckel","orcid":null,"position":16,"is_corresponding":false},{"id":1296271,"name":"Li Pang","orcid":"0000-0002-0212-2090","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T02:04:46.201722Z","pmid":"38547396","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":[]}