ArticleNature communications2022
Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity.
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Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51citing papers in PubMed
8.2field-weighted citation impact, top 2% of its field
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Who cites it
51 citing papers in PubMed, 56 citations in OpenAlex.
- Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer.Signal transduction and targeted therapy · 2026Trial
- Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study.Cell reports. Medicine · 2025Trial
- Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer.Journal for immunotherapy of cancer · 2026Article
- Asymmetric cross-reactivity of nuclear receptors reveals an evolutionary buffer between estrogen and androgen signaling.iScience · 2026Article
- The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals.bioRxiv : the preprint server for biology · 2026Article
- ATP-dependent chromatin remodelers in prostate cancer progression and therapeutic resistance.Endocrinology · 2026Review
- Increasing Cancer Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.bioRxiv : the preprint server for biology · 2026Article
- SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Ferroptosis vulnerability of enzalutamide resistant prostate cancer conferred by ACSL4 overexpression and GPX4 antagonism.Cell death & disease · 2026Article
- Prognostic biomarkers and Hedgehog pathway activation in early prostate cancer neuroendocrine differentiation via spatial profiling.NPJ precision oncology · 2026Article
- MECOM Function Is Critical for AR-Driven Treatment-Resistant Prostate Cancer.Cancer research · 2026Article
- Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer.Genome biology · 2026Article
- Role of the cross-regulation between Wnt pathway activation and androgen receptor signaling in prostate cancer treatment resistance.Cell death and differentiation · 2026Article
- SMARCA4 promotes lineage plasticity and enzalutamide resistance in prostate cancer by regulating PROX1 via H3K27 acetylation.Cell death discovery · 2026Article
- CDK12 Inactivation Attenuates Prostate Cancer Progression by Inhibiting BNIP3-Mediated Mitophagy.Cell proliferation · 2026Article
- Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.International journal of cancer · 2026Review
- Elevated Tumor-Associated Androgen Receptor Activity Correlates with Poor Immune Infiltration and Immunotherapy Response across Cancer Types.Cancer research communications · 2026Article
- Prostate cancer cells converge to an inflammatory-like state upon metastatic dissemination.Nature communications · 2025Article
- Unravelling TPX2-centered co-expression networks as key drivers of aggressive prostate cancer.Scientific reports · 2025Article
- Phase Ib study of enzalutamide with venetoclax in patients with metastatic castration-resistant prostate cancer.Cancer chemotherapy and pharmacology · 2025Article
Corrections and comments
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Authors and funding
37 authors at 12 institutions in 2 countries.
Thomas C Westbrook *Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Xiangnan Guan *Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Eva RodanskyDivision of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Diana FloresDivision of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Chia Jen LiuDepartment of Pathology, Michigan Center for Translational Pathology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Aaron M UdagerDepartment of Pathology, Michigan Center for Translational Pathology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Radhika A PatelDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Michael C HaffnerDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Ya-Mei HuKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.ORCID 0000-0002-2575-1770
Duanchen SunKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Tomasz M BeerKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.ORCID 0000-0001-5600-9993
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7003-7982
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Jack F YoungrenHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Charles J RyanMasonic Cancer Center, University of Minnesota; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Martin GleaveDepartment of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Yuzhuo WangDepartment of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-9749-8591
Jiaoti HuangDuke University, Durham, NC, USA.ORCID 0000-0003-1195-1998
Ilsa ColemanDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Colm MorrisseyDepartment of Urology, University of Washington, Seattle, WA, USA.
Peter S NelsonDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0002-5451-5726
Christopher P EvansUniversity of California Davis, Davis, CA, USA.
Primo LaraUniversity of California Davis, Davis, CA, USA.
Robert E ReiterUniversity of California Los Angeles, Los Angeles, CA, USA.
Owen WitteDepartment of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Matthew RettigUniversity of California Los Angeles, Los Angeles, CA, USA.
Christopher K WongUC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0001-6012-7001
Alana S WeinsteinUC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0002-1563-9072
Vlado UzunangelovUC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0002-1962-0977
Josh M StuartUC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0002-2171-565X
George V ThomasKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.ORCID 0000-0001-7416-8840
Felix Y FengHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0963-7687
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3191-6268
Joel A YatesDivision of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-1462-8494
Zheng XiaKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. xiaz@ohsu.edu.ORCID 0000-0003-3364-8324
Joshi J AlumkalDivision of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. jalumkal@med.umich.edu.ORCID 0000-0003-1278-0166
University of Michigan · USOregon Health & Science University · USUniversity of California, San Francisco · USFred Hutch Cancer Center · USUniversity of California, Santa Cruz · USUniversity of California, Los Angeles · USUniversity of California, Davis · USBC Cancer Agency · CADuke University · USUniversity of British Columbia · CAUniversity of Minnesota · USUniversity of Washington · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MTRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6MSteroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0MONCOLOGY RESEARCH TRAINING GRANTT32CA009357 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Qing Li · 1987 to 2026
$8.6MThe MSKCC-UW/Fred Hutch Prostate Cancer Drug Resistance and Sensitivity CenterU54CA224079 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SAWYERS, CHARLES L. · 2017 to 2021
$6.8MDefining and Targeting Lineage Transition Programs Operative in AR Pathway Independent Prostate CancerR01CA234715 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NELSON, PETER S · 2020 to 2024
$2.0MTargeting Prostate Cancer Lineage Plasticity with BET Bromodomain InhibitionR01CA251245 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALUMKAL, JOSHI JAMES · 2020 to 2024
$1.9MHaemAPA: Characterizing alternative polyadenylation in human blood cellsR21HL145426 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIA, ZHENG · 2019 to 2020
$231kNCI NIH HHS P01 CA163227NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA097186NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA234715NCI NIH HHS R01 CA251245NCI NIH HHS T32 CA009357NCI NIH HHS U54 CA224079NHLBI NIH HHS R21 HL145426
Abstract
The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which the tumors manifest reduced dependency on the AR. To improve our understanding of enza resistance, herein we analyze the transcriptomes of matched biopsies from men with metastatic CRPC obtained prior to treatment and at progression (n = 21). RNA-sequencing analysis demonstrates that enza does not induce marked, sustained changes in the tumor transcriptome in most patients. However, three patients' progression biopsies show evidence of lineage plasticity. The transcription factor E2F1 and pathways linked to tumor stemness are highly activated in baseline biopsies from patients whose tumors undergo lineage plasticity. We find a gene signature enriched in these baseline biopsies that is strongly associated with poor survival in independent patient cohorts and with risk of castration-induced lineage plasticity in patient-derived xenograft models, suggesting that tumors harboring this gene expression program may be at particular risk for resistance mediated by lineage plasticity and poor outcomes.
Indexed as
E2F1 Transcription FactorProstatic Neoplasms, Castration-ResistantAndrogen Receptor AntagonistsBenzamidesBiopsyCell Line, TumorDrug Resistance, NeoplasmHumansMaleNitrilesPhenylthiohydantoinReceptors, AndrogenRNAAndrogen Receptor AntagonistsBenzamidesE2F1 Transcription FactorenzalutamideNitrilesPhenylthiohydantoinReceptors, AndrogenRNA
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