Evidence map›Paper›PMID 39019980›Full record

ArticleProstate cancer and prostatic diseases2025

Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.

Amanda Broderick, Elizabeth Pan, Jinju Li, Alec Chu, Clara Hwang, Pedro C Barata, Frank Cameron Cackowski, Matthew Labriola, Alyssa Ghose, Mehmet Asim Bilen and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Amanda BroderickDuke Cancer Institute Center for Prostate and Urologic Cancers, Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.
Elizabeth PanMoores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Jinju LiRogel Cancer Center, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Alec ChuPathology Department, University of Michigan, Ann Arbor, MI, USA.
Clara HwangDivision of Hematology/Oncology, Department of Internal Medicine, Henry Ford Cancer Institute, Detroit, MI, USA.ORCID http://orcid.org/0000-0002-0998-323X
Pedro C BarataDepartment of Internal Medicine, University Hospitals Seidman Cancer Center, Cleveland, OH, USA.
Frank Cameron CackowskiBarbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.ORCID http://orcid.org/0000-0002-0075-3745
Matthew LabriolaDuke Cancer Institute Center for Prostate and Urologic Cancers, Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0919-9864
Alyssa GhoseDepartment of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
Mehmet Asim BilenWinship Cancer Institute of Emory University, Atlanta, GA, USA.
Deepak KilariDepartment of Medicine, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Bicky ThapaDepartment of Medicine, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Michael PieroDepartment of Medicine, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Laura GrahamUniversity of Colorado Cancer Center Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-4371-572X
Abhishek TripathiDepartment of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Rohan GarjeMiami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
Vadim S KoshkinUniversity of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Erik HernandezUniversity of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Tanya B DorffDepartment of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-5990-298X
Michael Thomas SchweizerUniversity of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5510-0661
Ajjai Shivaram AlvaDepartment of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
Rana R McKayMoores Cancer Center, University of California San Diego, La Jolla, CA, USA. mckay@ucsd.edu.ORCID http://orcid.org/0000-0002-0581-7963
Andrew J ArmstrongDuke Cancer Institute Center for Prostate and Urologic Cancers, Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA. andrew.armstrong@duke.edu.ORCID http://orcid.org/0000-0001-7012-1754

Funding

Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPCR01CA256157 · NCI · DUKE UNIVERSITY · PI ARMSTRONG, ANDREW J, DEHM, SCOTT M. · 2020 to 2025
$3.2M
Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancerR01CA233585 · NCI · DUKE UNIVERSITY · PI ARMSTRONG, ANDREW J · 2019 to 2023
$2.2M
NCI NIH HHS R01 CA256157U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01 1R01CA233585
6 · The paper itself

Abstract

backgroundAberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown.

methodsWe utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status.

resultsOf the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups.

conclusionsWnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.

Indexed as

Biomarkers, TumorMutationProstatic NeoplasmsWnt Signaling PathwayAdenomatous Polyposis Coli ProteinAgedbeta CateninHumansMaleMiddle AgedPrognosisRetinoblastoma Binding ProteinsRetrospective StudiesR-SpondinsUbiquitin-Protein LigasesAdenomatous Polyposis Coli ProteinAPC protein, humanbeta CateninBiomarkers, TumorCTNNB1 protein, humanRetinoblastoma Binding ProteinsRNF43 protein, humanRspo2 protein, humanR-SpondinsUbiquitin-Protein LigasesZNRF3 protein, human

Identifiers

PMID39019980
PMCPMC11739431

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.