Evidence map›Paper›PMID 41292858›Full record

ArticlebioRxiv : the preprint server for biology2025

NUAK2 is a therapeutically tractable regulator of RNA splicing and tumor progression in neuroendocrine prostate cancer.

Umar Mehraj, Uran Maimekov, Shaista Manzoor, Emily Cordova, Manasiben Patel, Ikeer Y Mancera-Ortiz, Stefanie Howell, Zachary W Davis-Gilbert, Mu-En Wang, Ming Chen and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Umar MehrajDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Uran MaimekovDepartment of Health Informatics, Rutgers School of Health Professions, Newark, NJ 07107, USA.
Shaista ManzoorDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Emily CordovaDepartment of Biology, Colorado State University Pueblo, Colorado, USA.
Manasiben PatelDepartment of Molecular Genetics and Microbiology Duke University, Durham, NC, USA.
Ikeer Y Mancera-OrtizStructural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Stefanie HowellStructural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Zachary W Davis-GilbertStructural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mu-En WangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Ming ChenDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Jung Wook ParkDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Yuzhuo WangVancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Andrew J ArmstrongDuke Cancer Institute, Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina, USA.
Jiaoti HuangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
David H DrewryStructural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Antonina MitrofanovaDepartment of Health Informatics, Rutgers School of Health Professions, Newark, NJ 07107, USA.
Everardo MaciasDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI Laura Fish · 1985 to 2026
$174.8M
NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA016086
6 · The paper itself

Abstract

Prostate cancer (PC) remains the second leading cause of cancer-related mortality in men. The emergence of treatment-emergent neuroendocrine prostate cancer (NEPC) arising from androgen receptor (AR) pathway inhibition poses a significant clinical challenge. Here, we report that NUAK family kinase 2 (NUAK2) is an actionable therapeutic target in NEPC. NUAK2 expression is markedly elevated in NEPC patient specimens and preclinical models, and its genetic or pharmacologic inhibition suppresses NEPC tumor growth. The FDA-approved CDK4/6 inhibitor trilaciclib exerts potent inhibition of NUAK2, leading to marked tumor suppression alone and enhanced efficacy in combination with carboplatin. Integrated phosphor-target and interactome analyses demonstrate that NUAK2 engages core spliceosome components to regulate pre-mRNA splicing. As proof of principle, we validated that NUAK2 inhibition perturbs pre-mRNA splicing of

Identifiers

PMID41292858
PMCPMC12642401

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.