Evidence map›Paper›PMID 42327601›Full record

ArticleSerican journal of medicine2025

Mechanisms and Therapeutic Strategies to Overcome Enzalutamide Resistance in Advanced Prostate Cancer.

Xinyi Wang, Zhiguo Li, Xiaoqi Liu

Abstract read
In one paragraph

Article in Serican journal of medicine, 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

3 authors.

Xinyi WangDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky 40536, USA.
Zhiguo LiDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky 40536, USA.
Xiaoqi LiuDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky 40536, USA.

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Jennifer F Rogers · 2013 to 2026
$38.3M
Plk1 in Chemo-resistance of CancerR01CA157429 · NCI · UNIVERSITY OF KENTUCKY · PI XIAOQI LIU · 2011 to 2026
$3.5M
Plk1 as a prognostic biomarker for prostate cancerR01CA264652 · NCI · UNIVERSITY OF KENTUCKY · PI LIU, XIAOQI · 2021 to 2025
$2.7M
Targeting the Plk1/Pdcd4/mTORC2 Signaling to Treat Castration-Resistant Prostate CancerR01CA272483 · NCI · UNIVERSITY OF KENTUCKY · PI XIAOQI LIU, Hsin-Sheng Yang · 2023 to 2026
$2.5M
Enhancing the efficacy of androgen signaling inhibitors in prostate cancerR01CA256893 · NCI · UNIVERSITY OF KENTUCKY · PI LIU, XIAOQI · 2021 to 2025
$2.4M
Targeting Polo-Like Kinase 1 in Prostate Cancer to Enhance Therapeutic EfficacyR01CA266579 · NCI · UNIVERSITY OF KENTUCKY · PI Zhiguo Li · 2022 to 2026
$2.2M
NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA157429NCI NIH HHS R01 CA256893NCI NIH HHS R01 CA264652NCI NIH HHS R01 CA266579NCI NIH HHS R01 CA272483
6 · The paper itself

Abstract

Enzalutamide, a second-generation androgen receptor (AR) inhibitor, has significantly improved survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). However, resistance to enzalutamide emerges in nearly all patients, posing a major clinical challenge. This review comprehensively examines the multifaceted mechanisms underlying enzalutamide resistance, including AR amplification, point mutations, splice variants such as AR-V7, and the activation of bypass signaling pathways, including glucocorticoid receptor signaling, PI3K/Akt/mTOR, and Wnt signaling. Additionally, the tumor microenvironment, lineage plasticity, and neuroendocrine differentiation contribute to therapy resistance through immune evasion and epigenetic reprogramming. We further discuss promising therapeutic strategies aimed at overcoming resistance, including combination treatments with PARP inhibitors, epigenetic modulators, and next-generation androgen receptor (AR) inhibitors. Biomarkers and personalized medicine approaches increasingly guide ongoing clinical trials to optimize treatment efficacy. This review also highlights drug repurposing as a practical avenue for targeting noncanonical vulnerabilities in resistant prostate cancer. Together, these insights provide a foundation for developing more durable and individualized treatment strategies for patients with enzalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC).

Indexed as

Castration resistanceEnzalutamide resistanceprostate cancer

Identifiers

PMID42327601
PMCPMC13278092

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.