2. Academic Validation
  3. Identification of PRDX5 as A Target for The Treatment of Castration-Resistant Prostate Cancer

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

  • Adv Sci (Weinh). 2023 Dec 20:e2304939. doi: 10.1002/advs.202304939.
Rong Wang 1 2,  Yuanyuan Mi 3,  Jiang Ni 3,  Yang Wang 1,  Lingwen Ding 4 5,  Xuebin Ran 4 5,  Qiaoyang Sun 6,  Soo Yong Tan 4,  H Phillip Koeffler 5 7,  Ninghan Feng 1,  Yong Q Chen 1 2
Affiliations

Affiliations

  • 1 Jiangnan University Medical Center, Jiangnan University, Wuxi, 214002, China.
  • 2 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
  • 3 Affiliated Hospital, Jiangnan University, Wuxi, 214122, China.
  • 4 Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
  • 5 Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • 6 Department of Hematology, Singapore General Hospital, Singapore, 169608, Singapore.
  • 7 Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, 90048, USA.
PMID: 38115765 DOI: 10.1002/advs.202304939
Abstract

Treatment of castration-resistant prostate Cancer (CRPC) is a long-standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking Androgen Receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug-tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up-regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration-resistant prostate Cancer.

Keywords

castration-resistant prostate cancer; drug-tolerant persister; peroxiredoxin 5; polaprezinc; stachyose.

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