{"doi":"10.3390/cells14030169","title":"Role of GPCR Signaling in Anthracycline-Induced Cardiotoxicity","abstract":"Anthracyclines are a class of chemotherapeutics commonly used to treat a range of cancers. Despite success in improving cancer survival rates, anthracyclines have dose-limiting cardiotoxicity that prevents more widespread clinical utility. Currently, the therapeutic options for these patients are limited to the iron-chelating agent dexrazoxane, the only FDA-approved drug for anthracycline cardiotoxicity. However, the clinical use of dexrazoxane has failed to replicate expectations from preclinical studies. A limited list of GPCRs have been identified as pathogenic in anthracycline-induced cardiotoxicity, including receptors (frizzled, adrenoreceptors, angiotensin II receptors) previously implicated in cardiac remodeling in other pathologies. The RNA sequencing of iPSC-derived cardiac myocytes from patients has increased our understanding of the pathogenic mechanisms driving cardiotoxicity. These data identified changes in the expression of novel GPCRs, heterotrimeric G proteins, and the regulatory pathways that govern downstream signaling. This review will capitalize on insights from these experiments to explain aspects of disease pathogenesis and cardiac remodeling. These data provide a cornucopia of possible unexplored potential pathways by which we can reduce the cardiotoxic side effects, without compromising the anti-cancer effects, of doxorubicin and provide new therapeutic options to improve the recovery and quality of life for patients undergoing chemotherapy.","journal":"Cells","year":2025,"id":537889,"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":0.9532,"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":1377537,"name":"Ritika Harish","orcid":null,"position":1,"is_corresponding":false},{"id":1424591,"name":"Minahil Roshan","orcid":null,"position":2,"is_corresponding":false},{"id":1424592,"name":"Sathvik Samudrala","orcid":null,"position":3,"is_corresponding":false},{"id":420808,"name":"Xuanmao Jiao","orcid":"0000-0003-4222-9172","position":4,"is_corresponding":false},{"id":420813,"name":"Richard G. Pestell","orcid":"0000-0003-3244-8777","position":5,"is_corresponding":false},{"id":503647,"name":"Anthony W. Ashton","orcid":"0000-0001-6063-1566","position":6,"is_corresponding":false},{"id":1424590,"name":"Nimish Biswal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":269,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39936961","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":[]}