{"doi":"10.17615/3s83-jf70","title":"Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse","abstract":"Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a pro-inflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells non-specifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T-cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anti-cancer treatments.","journal":"UNC Libraries","year":2020,"id":143284,"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":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":608042,"name":"Shani Alston","orcid":"0000-0002-9823-5398","position":1,"is_corresponding":false},{"id":611371,"name":"Monique N. O’Leary","orcid":null,"position":2,"is_corresponding":false},{"id":237881,"name":"Daohong Zhou","orcid":"0000-0002-2400-6461","position":3,"is_corresponding":false},{"id":349846,"name":"Allison M. Deal","orcid":"0000-0003-3526-3938","position":4,"is_corresponding":false},{"id":262852,"name":"Alexis Valdovinos","orcid":"0000-0003-4815-7974","position":5,"is_corresponding":false},{"id":528939,"name":"Natalia Mitin","orcid":"0000-0003-4898-7716","position":6,"is_corresponding":false},{"id":250397,"name":"Fatouma Alimirah","orcid":"0000-0002-3597-5807","position":7,"is_corresponding":false},{"id":336497,"name":"Alain de Bruin","orcid":"0000-0001-8579-2649","position":8,"is_corresponding":false},{"id":511546,"name":"Kristin L Koenig","orcid":"0000-0002-2071-3169","position":9,"is_corresponding":false},{"id":228995,"name":"Brian K. Kennedy","orcid":"0000-0002-5754-1874","position":10,"is_corresponding":false},{"id":535400,"name":"Hyman B. Muss","orcid":"0000-0003-2862-9970","position":11,"is_corresponding":false},{"id":237865,"name":"Jianhui Chang","orcid":"0000-0002-8855-8521","position":12,"is_corresponding":false},{"id":610919,"name":"Su Liu","orcid":"0000-0001-5805-5643","position":13,"is_corresponding":false},{"id":326012,"name":"Lijian Shao","orcid":"0000-0002-7000-7094","position":14,"is_corresponding":false},{"id":85400,"name":"Norman E. Sharpless","orcid":"0000-0001-7078-9455","position":15,"is_corresponding":false},{"id":610920,"name":"Emmeline C. Academia","orcid":"0000-0001-7514-1754","position":16,"is_corresponding":false},{"id":106306,"name":"Judith Campisi","orcid":"0000-0001-6858-9462","position":17,"is_corresponding":false},{"id":262856,"name":"Marco Demaria","orcid":"0000-0002-8429-4813","position":18,"is_corresponding":false},{"id":611372,"name":"Sumner Kilmarx","orcid":null,"position":19,"is_corresponding":false},{"id":596827,"name":"Catherine Le","orcid":null,"position":20,"is_corresponding":false},{"id":610921,"name":"Simon Melov","orcid":"0000-0001-8554-2834","position":21,"is_corresponding":false},{"id":610918,"name":"Boshi Wang","orcid":"0000-0002-9257-6714","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:38.432803Z","pmid":null,"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":[]}