{"doi":"10.17615/hett-8q86","title":"Combating subclonal evolution of resistant cancer phenotypes","abstract":"Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves.","journal":"UNC Libraries","year":2020,"id":143939,"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":0.953,"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":35166,"name":" Aaron R. Quinlan ","orcid":"0000-0003-1756-0859","position":1,"is_corresponding":false},{"id":317426,"name":"Rachel E. Factor","orcid":"0000-0003-1388-2500","position":2,"is_corresponding":false},{"id":231453,"name":"Ryan M. Layer","orcid":"0000-0002-5823-3232","position":3,"is_corresponding":false},{"id":612445,"name":"Layla A. Anderson","orcid":null,"position":4,"is_corresponding":false},{"id":611981,"name":"David F. Jenkins","orcid":"0000-0002-7451-4288","position":5,"is_corresponding":false},{"id":611982,"name":"Yi Qiao","orcid":"0009-0002-4807-0633","position":6,"is_corresponding":false},{"id":552821,"name":"Theresa L. Werner","orcid":"0000-0003-3868-7795","position":7,"is_corresponding":false},{"id":566453,"name":"Gajendra Shrestha","orcid":"0000-0001-6525-7913","position":8,"is_corresponding":false},{"id":258885,"name":"Brent S. Pedersen","orcid":"0000-0003-1786-2216","position":9,"is_corresponding":false},{"id":225103,"name":"Joe W. Gray","orcid":"0000-0001-9225-6756","position":10,"is_corresponding":false},{"id":54991,"name":"Gábor Marth","orcid":"0000-0003-0222-1694","position":11,"is_corresponding":false},{"id":489778,"name":"Stephen Piccolo","orcid":"0000-0003-2001-5640","position":12,"is_corresponding":false},{"id":105532,"name":"W. Evan Johnson","orcid":"0000-0002-6247-6595","position":13,"is_corresponding":false},{"id":447323,"name":"Dean Y. Li","orcid":"0000-0002-8758-6619","position":14,"is_corresponding":false},{"id":13902,"name":"Joel S. Parker","orcid":"0000-0003-2080-6901","position":15,"is_corresponding":false},{"id":611983,"name":"R.H. Miller","orcid":"0000-0003-1674-7929","position":16,"is_corresponding":false},{"id":393343,"name":"Philip J. Moos","orcid":"0000-0002-8223-442X","position":17,"is_corresponding":false},{"id":551193,"name":"Chakravarthy B. Reddy","orcid":null,"position":18,"is_corresponding":false},{"id":497124,"name":"Adam L. Cohen","orcid":"0000-0003-0591-1009","position":19,"is_corresponding":false},{"id":449639,"name":"Andrea H. Bild","orcid":"0000-0001-7906-6675","position":20,"is_corresponding":false},{"id":225504,"name":"Saundra S. Buys","orcid":"0000-0003-4120-5697","position":21,"is_corresponding":false},{"id":252136,"name":"Samuel W. Brady","orcid":"0000-0001-5518-7800","position":22,"is_corresponding":false},{"id":338246,"name":"Jonathan Boltax","orcid":null,"position":23,"is_corresponding":false},{"id":411104,"name":"Jasmine A. McQuerry","orcid":"0000-0002-0702-9709","position":24,"is_corresponding":false},{"id":611984,"name":"Amanda Esch","orcid":"0000-0002-4355-7162","position":25,"is_corresponding":false},{"id":1893,"name":"Laura M. Heiser","orcid":"0000-0003-3330-0950","position":26,"is_corresponding":false},{"id":445381,"name":"Sara R. Selitsky","orcid":"0000-0001-8765-5269","position":27,"is_corresponding":false},{"id":302,"name":"Brian K. Dalley","orcid":"0009-0003-9774-5200","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","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":[]}