{"doi":"10.1016/j.cell.2025.07.042","title":"Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers","abstract":"Advanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic). Tumor androgen receptor signaling is associated with longer survival, whereas increased proliferation predicted shorter survival. In a pre-specified analysis, the previously identified decipher RNA signature was both prognostic and predicted survival benefit from docetaxel for metastatic cancers (biomarker-docetaxel interaction p = 0.039). Additionally, transcriptome-based classification of PTEN inactivation identified tumors more likely to have PTEN protein loss ( p = 4 × 10 −37 ) and metabolically perturbed metastatic cancers that had shorter survival with hormone therapies ( p < 0.001) but exhibited docetaxel sensitivity (biomarker-docetaxel interaction p = 0.002). Transcriptome classifiers predict docetaxel benefit and could be clinically implemented for improved patient management.","journal":"Cell","year":2025,"id":510024,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"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":1365289,"name":"Peter Dutey‐Magni","orcid":"0000-0002-8942-9836","position":1,"is_corresponding":false},{"id":888057,"name":"Marina Parry","orcid":"0000-0003-3278-9491","position":2,"is_corresponding":false},{"id":888056,"name":"Larissa Mendes","orcid":"0000-0002-2417-1109","position":3,"is_corresponding":false},{"id":1365290,"name":"Ashwin Sachdeva","orcid":"0000-0002-7359-7114","position":4,"is_corresponding":false},{"id":1071558,"name":"James A. Proudfoot","orcid":"0009-0008-7063-5761","position":5,"is_corresponding":false},{"id":367158,"name":"Anis Hamid","orcid":"0000-0002-7193-9723","position":6,"is_corresponding":false},{"id":1365291,"name":"Mazlina Ismail","orcid":"0000-0002-1514-3819","position":7,"is_corresponding":false},{"id":1325572,"name":"Sarah Howlett","orcid":"0000-0002-2157-8819","position":8,"is_corresponding":false},{"id":888054,"name":"Stefanie Friedrich","orcid":"0000-0002-3889-5589","position":9,"is_corresponding":false},{"id":1054961,"name":"Lia DePaula Oliveira","orcid":"0009-0005-5274-8453","position":10,"is_corresponding":false},{"id":1365292,"name":"Laura Murphy","orcid":"0000-0002-7409-931X","position":11,"is_corresponding":false},{"id":888055,"name":"Chris Brawley","orcid":"0000-0003-3641-278X","position":12,"is_corresponding":false},{"id":1054960,"name":"Oluwademilade Dairo","orcid":"0009-0004-8362-8430","position":13,"is_corresponding":false},{"id":888701,"name":"Sharanpreet Lall","orcid":null,"position":14,"is_corresponding":false},{"id":331715,"name":"Yang Liu","orcid":"0000-0002-0367-8189","position":15,"is_corresponding":false},{"id":632483,"name":"Daniel Wetterskog","orcid":"0000-0003-4163-6438","position":16,"is_corresponding":false},{"id":888062,"name":"Anna Wingate","orcid":"0009-0008-4965-7093","position":17,"is_corresponding":false},{"id":1365293,"name":"Karolina Nowakowska","orcid":"0000-0003-0584-7895","position":18,"is_corresponding":false},{"id":888702,"name":"Leila Zakka","orcid":null,"position":19,"is_corresponding":false},{"id":1366063,"name":"Claire Amos","orcid":null,"position":20,"is_corresponding":false},{"id":1125867,"name":"Nafisah B Atako","orcid":null,"position":21,"is_corresponding":false},{"id":32007,"name":"Victoria Wang","orcid":null,"position":22,"is_corresponding":false},{"id":1365294,"name":"Hannah Rush","orcid":"0000-0001-9550-8808","position":23,"is_corresponding":false},{"id":856579,"name":"Robert J. Jones","orcid":"0000-0002-2904-6980","position":24,"is_corresponding":false},{"id":42039,"name":"Hing Y. Leung","orcid":"0000-0002-3933-3975","position":25,"is_corresponding":false},{"id":305602,"name":"William Cross","orcid":"0000-0001-9276-3053","position":26,"is_corresponding":false},{"id":652202,"name":"Silke Gillessen","orcid":"0000-0001-5746-6555","position":27,"is_corresponding":false},{"id":1067481,"name":"Chris Parker","orcid":"0000-0001-6512-124X","position":28,"is_corresponding":false},{"id":235940,"name":"Teresa Marafioti","orcid":"0000-0003-1223-6275","position":29,"is_corresponding":false},{"id":351011,"name":"Alfonso Urbanucci","orcid":"0000-0003-2931-3652","position":30,"is_corresponding":false},{"id":13455,"name":"Matthew W. Fittall","orcid":"0000-0002-5172-4100","position":31,"is_corresponding":false},{"id":272252,"name":"Edward M. Schaeffer","orcid":"0000-0003-0699-1899","position":32,"is_corresponding":false},{"id":262580,"name":"Daniel E. Spratt","orcid":"0000-0002-5973-4741","position":33,"is_corresponding":false},{"id":900533,"name":"David Waugh","orcid":"0000-0002-4022-3765","position":34,"is_corresponding":false},{"id":229488,"name":"Thomas Powles","orcid":null,"position":35,"is_corresponding":false},{"id":858811,"name":"Matthew R. Sydes","orcid":"0000-0002-9323-1371","position":36,"is_corresponding":false},{"id":259327,"name":"Felix Y. Feng","orcid":"0000-0002-0963-7687","position":37,"is_corresponding":false},{"id":13255,"name":"Daniel M. Berney","orcid":"0000-0001-5474-8696","position":38,"is_corresponding":false},{"id":682428,"name":"Mahesh Parmar","orcid":"0000-0003-0166-1700","position":39,"is_corresponding":false},{"id":888065,"name":"Noel W. Clarke","orcid":"0000-0001-7776-8059","position":40,"is_corresponding":false},{"id":418626,"name":"Elai Davicioni","orcid":"0000-0001-9136-099X","position":41,"is_corresponding":false},{"id":323563,"name":"Tamara L. Lotan","orcid":"0000-0002-0494-9067","position":42,"is_corresponding":false},{"id":342648,"name":"Christopher J. Sweeney","orcid":"0000-0002-0398-6018","position":43,"is_corresponding":false},{"id":888066,"name":"Louise Brown","orcid":"0000-0003-2827-6634","position":44,"is_corresponding":false},{"id":305609,"name":"Nicholas D. James","orcid":"0000-0002-7314-8204","position":45,"is_corresponding":false},{"id":554640,"name":"Gerhardt Attard","orcid":"0000-0002-4811-7983","position":46,"is_corresponding":false},{"id":888699,"name":"Emily Grist","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40865526","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":[]}