Evidence map›Paper›PMID 40624104›Full record

ArticleNPJ precision oncology2025

Transcriptional profiling clarifies a program of enzalutamide extreme non-response in lethal prostate cancer.

Anbarasu Kumaraswamy, Ya-Mei Hu, Joel A Yates, Chao Zhang, Eva Rodansky, Dhruv Khokhani, Diana Flores, Zhi Duan, Yi Zhang, Shaadi Tabatabaei and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

31 authors.

Anbarasu Kumaraswamy *Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Ya-Mei Hu *Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
Joel A Yates *Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Chao ZhangDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Eva RodanskyDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Dhruv KhokhaniDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Diana FloresDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Zhi DuanDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Yi ZhangDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
Shaadi TabatabaeiKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Rachel SlottkeKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Shangyuan YeBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Primo LaraUniversity of California Davis, Davis, CA, USA.
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Charles J RyanMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Jiaoti HuangDuke University, Durham, NC, USA.
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Robert E ReiterDepartments of Medicine and Urology, University of California Los Angeles, Los Angeles, CA, USA.
Max S WichaDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Tomasz M BeerKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Matthew RettigDepartments of Medicine and Urology, University of California Los Angeles, Los Angeles, CA, USA.
Martin GleaveDepartment of Urological Sciences, University of British Columbia, Vancouver, BC, Canada.
Christopher P EvansUniversity of California Davis, Davis, CA, USA.
Owen N WitteDepartment of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Joshua M StuartGenomics Institute and Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
George V ThomasKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Felix Y FengHelen Diller Family Comprehensive Cancer Center, 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.
Zheng XiaDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA. xiaz@ohsu.edu.
Joshi J AlumkalDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. jalumkal@med.umich.edu.

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6M
PORT (Portland Oral health Research Training)T90DE030859 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI WU, HUI · 2021 to 2025
$2.1M
Targeting Prostate Cancer Lineage Plasticity with BET Bromodomain InhibitionR01CA251245 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALUMKAL, JOSHI JAMES · 2020 to 2024
$1.9M
Developing New Treatment Strategies for Neuroendocrine Prostate CancerR01CA282005 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joshi James Alumkal · 2024 to 2026
$1.6M
Characterizing phenotype-associated subpopulations from single-cell sequencing dataR01GM147365 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Zheng Xia · 2023 to 2026
$1.2M
Targeting Early Drivers of Prostate Cancer Lineage PlasticityR01CA291986 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joshi James Alumkal · 2025 to 2026
$1.0M
NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA251245NCI NIH HHS R01CA251245, R01CA282005, P50 CA186786, P30CA046592,R01CA291986NCI NIH HHS R01 CA282005NCI NIH HHS R01 CA291986NIDCR NIH HHS T90 DE030859NIGMS NIH HHS R01 GM147365NIGMS NIH HHS R01GM147365NIH HHS T90 DE030859Stand Up to Cancer-Prostate Cancer Foundation (PCF) Prostate Dream Team Translational Cancer Research Grant SU2C-AACR-DT0409U.S. Department of Defense W81XWH2110539
6 · The paper itself

Abstract

The androgen receptor inhibitor enzalutamide is one of the principal treatments for metastatic prostate cancer. Most patients respond. However, a subset is primary refractory. Seeking to understand enzalutamide extreme non-response (ENR), we analyzed RNA-sequencing in biopsies from men treated prospectively on an enzalutamide clinical trial. We focused on those with ENR (progression within 3 months) vs. long-term response (progression after 24 months). We identified an ENR program linked to proliferation, epithelial-to-mesenchymal transition, and stemness. High expression of this program in additional datasets was independently linked to poor tumor control with AR targeting but favorable tumor control with docetaxel, another standard treatment. CDK2 was implicated in the ENR program. CDK2 suppression reduced the ENR program and viability of ENR program-high prostate cancer models. The ENR gene program is predictive of non-response to AR targeting. Patients whose tumors harbor this program may be good candidates for docetaxel or CDK2 inhibitor clinical trials.

Identifiers

PMID40624104
PMCPMC12234718

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