Evidence map›Paper›PMID 30928160›Full record

ArticleEuropean urology2019

Genomic Drivers of Poor Prognosis and Enzalutamide Resistance in Metastatic Castration-resistant Prostate Cancer.

William S Chen, Rahul Aggarwal, Li Zhang, Shuang G Zhao, George V Thomas, Tomasz M Beer, David A Quigley, Adam Foye, Denise Playdle, Jiaoti Huang and 19 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 2 pooled it
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Single-Cell Circulating Tumor Cell Analysis Reveals Genomic Instability as a Distinctive Feature of Aggressive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  4. Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Trial
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Racial variation in the advanced prostate cancer genome.Prostate cancer and prostatic diseases · 2025
    Article
  12. Article
  13. Article
  14. CBP/p300, a promising therapeutic target for prostate cancer.Journal of translational medicine · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Metabolic and imaging phenotypes associated withbioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 10 institutions in 2 countries.

William S ChenHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Yale School of Medicine, New Haven, CT, USA.
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Li ZhangHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Shuang G ZhaoUniversity of Michigan, Ann Arbor, MI, USA.
George V ThomasKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Tomasz M BeerKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Denise PlaydleHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Jiaoti HuangDuke University, Durham, NC, USA.
Paul LloydHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Eric LuKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Duanchen SunKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Xiangnan GuanKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Matthew RettigUniversity of California Los Angeles, Los Angeles, CA, USA; VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Martin GleaveUniversity of British Columbia, Vancouver, Canada.
Christopher P EvansUniversity of California Davis, Davis, CA, USA.
Jack YoungrenHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lawrence TrueUniversity of Washington, Seattle, WA, USA.
Primo LaraUniversity of California Davis, Davis, CA, USA.
Vishal KothariHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Zheng XiaKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Kim N ChiUniversity of British Columbia, Vancouver, Canada.
Robert E ReiterUniversity of California Los Angeles, Los Angeles, CA, USA.
Christopher A MaherWashington University in St. Louis, St. Louis, MO, USA.
Felix Y FengHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Departments of Radiation Oncology and Urology, University of California San Francisco, San Francisco, CA, USA.
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Electronic address: eric.small@ucsf.edu.
Joshi J AlumkalKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
West Coast Prostate Cancer Dream Team
University of California, San Francisco · USOregon Health & Science University · USUCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of California, Davis · USUniversity of British Columbia · CADuke University · USUniversity of California, Los Angeles · USUniversity of Michigan · USUniversity of Washington · USVA Greater Los Angeles Healthcare System · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1M
In Silico Screening of Alternative Polyadenylation Regulators in CancersK01LM012877 · NLM · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIA, ZHENG · 2018 to 2020
$428k
NCI NIH HHS P30 CA014236NCI NIH HHS P50 CA097186NLM NIH HHS K01 LM012877
6 · The paper itself

Abstract

backgroundMetastatic castration-resistant prostate cancer (mCRPC) is the lethal form of the disease. Several recent studies have identified genomic alterations in mCRPC, but the clinical implications of these genomic alterations have not been fully elucidated.

objectiveTo use whole-genome sequencing (WGS) to assess the association between key driver gene alterations and overall survival (OS), and to use whole-transcriptome RNA sequencing to identify genomic drivers of enzalutamide resistance. DESIGN, SETTING, AND

participantsWe performed survival analyses and gene set enrichment analysis (GSEA) on WGS and RNA sequencing results for a cohort of 101 mCRPC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS was the clinical endpoint for all univariate and multivariable survival analyses. Candidate drivers of enzalutamide resistance were identified in an unbiased manner, and mutations of the top candidate were further assessed for enrichment among enzalutamide-resistant patients using Fisher's exact test. RESULTS AND LIMITATIONS: Harboring two DNA alterations in RB1 was independently predictive of poor OS (median 14.1 vs 42.0mo; p=0.007) for men with mCRPC. GSEA identified the Wnt/β-catenin pathway as the top differentially modulated pathway among enzalutamide-resistant patients. Furthermore, β-catenin mutations were exclusive to enzalutamide-resistant patients (p=0.01) and independently predictive of poor OS (median 13.6 vs 41.7mo; p=0.025).

conclusionsThe presence of two RB1 DNA alterations identified in our WGS analysis was independently associated with poor OS among men with mCRPC. The Wnt/β-catenin pathway plays an important role in enzalutamide resistance, with differential pathway expression and enrichment of β-catenin mutations in enzalutamide-resistant patients. Moreover, β-catenin mutations were predictive of poor OS in our cohort. PATIENT SUMMARY: We observed a correlation between genomic findings for biopsy samples from metastases from men with metastatic castration-resistant prostate cancer (mCRPC) and clinical outcomes. This work sheds new light on clinically relevant genomic alterations in mCRPC and provides a roadmap for the development of new personalized treatment regimens in mCRPC.

Indexed as

Neoplasm MetastasisProstatic Neoplasms, Castration-ResistantAgedAntineoplastic AgentsBenzamidesBiomarkers, TumorDrug Resistance, NeoplasmHumansMaleMiddle AgedNeoplasm StagingNitrilesOutcome Assessment, Health CarePhenylthiohydantoinPredictive Value of TestsPrognosisAntineoplastic AgentsBenzamidesBiomarkers, TumorenzalutamideNitrilesPhenylthiohydantoinProstate-Specific AntigenAdvanced prostate cancerCastration-resistantClinical outcomesEnzalutamideGenomicsMetastatic prostate cancerPrognostic factors

Identifiers

PMID30928160
PMCPMC6764911
OpenAlexW2926592082

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.