Evidence map›Paper›PMID 40211483›Full record

ArticleThe Prostate2025

Understanding Enzalutamide-Resistance Based on a Functional Single-Cell Approach.

Changhui Xue, Hyun-Kyung Ko, Kasen Shi, Janet Pittsenbarger, Lucien Vu Dao, Kaiyo Shi, Maximilian Libmann, Hao Geng, David Z Qian

Abstract read
In one paragraph

Article in The Prostate, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Changhui XueDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Hyun-Kyung KoDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.ORCID 0000-0002-7896-362X
Kasen ShiDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Janet PittsenbargerDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Lucien Vu DaoDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Kaiyo ShiDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Maximilian LibmannDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Hao GengDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
David Z QianDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.ORCID 0000-0002-5532-2432

Funding

Adaptive resistance to HIF1a inhibition in hypoxiaR01CA207377 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI QIAN, ZHENG DAVID · 2016 to 2020
$1.8M
Developing therapies to improve enzalutamide in CRPCR01CA270271 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI QIAN, ZHENG DAVID · 2023 to 2025
$1.2M
HIF1a N-terminus hyperacetylation and anticancer mechanism of hydroxamic-HDACiR01CA149253 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI QIAN, ZHENG DAVID · 2010 to 2014
$1.1M
Adaptive resistance to AR inhibitors in hypoxia by GPT1R01CA279964 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Zheng David Qian · 2023 to 2026
$1.1M
NCI NIH HHS R01 CA149253NCI NIH HHS R01 CA207377NCI NIH HHS R01 CA270271NCI NIH HHS R01 CA279964This study is supported by NIH/NCI grants 5R01CA149253 and 5R01CA207377 to D.Z.Q.
6 · The paper itself

Abstract

backgroundAnti-androgen or castration therapies are the mainstay treatment for metastatic prostate cancers (PCa). Although effective at first, androgen-dependent PCa (ADPC) universally develops therapy resistance, thereby evolving into an incurable disease called castration-resistant PCa (CRPC). Currently, mechanisms underlying the emergence of CRPC from ADPC are largely unclear.

methodsWe used single-cell RNA-sequencing (scRNA-Seq) to determine the transcription heterogeneity of a therapy-naïve ADPC cell line-LNCaP and how it responded to the anti-androgen drug, enzalutamide. Based on the results, we used single-cell/colony-based cloning to isolate a pre-enzalutamide cell subset, displaying low and/or no expression of androgen receptor (AR

resultsWe found that most LNCaP cells expressed enzalutamide-target androgen receptor (AR+), while a small subpopulation (~10%) expressed low or no AR (AR

conclusionIn summary, our single-cell-based sequencing and functional tests suggest a clonal selection and expansion model of enzalutamide resistance, in which the pretreatment AR-low subpopulation is selected and expanded to confer treatment resistance.

Indexed as

Drug Resistance, NeoplasmPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantAnimalsBenzamidesCell Line, TumorHumansMaleMiceNitrilesReceptors, AndrogenSingle-Cell AnalysisXenograft Model Antitumor AssaysAR protein, humanBenzamidesenzalutamideNitrilesPhenylthiohydantoinReceptors, Androgenandrogen receptorcastration resistanceenzalutamideprostate cancersingle‐cell RNA‐Seq

Identifiers

PMID40211483
PMCPMC12768086

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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.