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

Author:

Wang Rong12,Mi Yuanyuan3,Ni Jiang3,Wang Yang1,Ding Lingwen45,Ran Xuebin45,Sun Qiaoyang6,Tan Soo Yong4,Koeffler H Phillip57,Feng Ninghan1,Chen Yong Q12ORCID

Affiliation:

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

Abstract

AbstractTreatment 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.

Funder

National Medical Research Council

Jiangsu Provincial Key Research and Development Program

Major Research Plan

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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