Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers.
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Date
2025
Authors
Grist, E.
Dutey-Magni, P.
Parry, M.A.
Mendes, L.
Sachdeva, A.
Proudfoot, J.A.
Hamid, A.A.
Ismail, M.
Howlett, S.
Friedrich, S.
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Journal article
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Cell, 2025; 188(20):1-29
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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.
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Data source: supplementary information, https://doi.org/10.1016/j.cell.2025.07.042
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Copyright 2025 The Authors. (http://creativecommons.org/licenses/by/4.0/)
Access Condition Notes: This is an open access article under the CC BY license