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Updated: Jul 8, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

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Identification of PRDX5 as A Target for The Treatment of Castration-Resistant Prostate Cancer

Rong Wang1,2, Yuanyuan Mi3, Jiang Ni3

  • 1Jiangnan University Medical Center, Jiangnan University, Wuxi, 214002, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 20, 2023
PubMed

Insights

Androgen receptor (AR) inhibitor treatment causes a drug-tolerant persister (DTP) state in castration-resistant prostate cancer (CRPC). Inhibiting Peroxiredoxin 5 (PRDX5) suppresses DTP cells and CRPC progression, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) presents a significant clinical challenge.
  • Current treatments target dihydrotestosterone biosynthesis or androgen receptor (AR) signaling.

Purpose of the Study:

  • To investigate the mechanisms of resistance to AR inhibitor therapy in CRPC.
  • To identify novel therapeutic targets for managing CRPC.

Main Methods:

  • Induction of a drug-tolerant persister (DTP) state in CRPC cells.
  • Analysis of the thioredoxin/peroxiredoxin pathway in DTP cells.
  • Inhibition of Peroxiredoxin 5 (PRDX5) in vitro and in vivo models.
  • Evaluation of PRDX5 inhibition on patient tumor progression.

Main Results:

  • AR inhibitor treatment leads to the emergence of a DTP state.
  • The thioredoxin/peroxiredoxin pathway, specifically PRDX5, is upregulated in DTP cells.
  • PRDX5 inhibition suppressed DTP cell proliferation, CRPC development in animal models, and stabilized PSA progression and metastatic lesions in patients.

Conclusions:

  • PRDX5 plays a crucial role in promoting AR inhibitor resistance and CRPC progression.
  • Targeting PRDX5 represents a novel therapeutic strategy for CRPC management.
Keywords:
castration-resistant prostate cancerdrug-tolerant persisterperoxiredoxin 5polaprezincstachyose

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