New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic

Neuroendocrine prostate cancer (NEPC), an aggressive and highly malignant subtype of castration-resistant prostate cancer (CRPC), arises through drug resistance mechanisms involving genomic alterations, epigenetic remodeling, tumor microenvironment (TME) reprogramming, and lineage plasticity. A hall...

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Main Authors: Maoping Cai, Fengtao Zheng, Yang-Zi Ren, Chuqian Zhen, Dujiang Fu, Xian-Lu Song, Qing Li, Yuanyuan Qu, Zhe-Sheng Chen, Shan-Chao Zhao
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0791
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author Maoping Cai
Fengtao Zheng
Yang-Zi Ren
Chuqian Zhen
Dujiang Fu
Xian-Lu Song
Qing Li
Yuanyuan Qu
Zhe-Sheng Chen
Shan-Chao Zhao
author_facet Maoping Cai
Fengtao Zheng
Yang-Zi Ren
Chuqian Zhen
Dujiang Fu
Xian-Lu Song
Qing Li
Yuanyuan Qu
Zhe-Sheng Chen
Shan-Chao Zhao
author_sort Maoping Cai
collection DOAJ
description Neuroendocrine prostate cancer (NEPC), an aggressive and highly malignant subtype of castration-resistant prostate cancer (CRPC), arises through drug resistance mechanisms involving genomic alterations, epigenetic remodeling, tumor microenvironment (TME) reprogramming, and lineage plasticity. A hallmark of NEPC is its independence from the androgen receptor (AR) pathway, evidenced by diminished or absent AR expression—a key barrier to effective clinical management. Therefore, a comprehensive understanding of NEPC pathogenesis and progression is essential, as it facilitates the identification of potential therapeutic targets and the development of more effective therapies. In this review, we summarize the typical characteristics of NEPC and describe its clinical diagnosis, relevant imaging modalities, current treatment strategies, and associated therapeutic difficulties. We also highlight the core events driving NEPC formation. Furthermore, we discuss potential therapeutic targets for the disease and review pharmacological agents that have demonstrated efficacy against NEPC, aiming to offer innovative perspectives and potential research directions for future NEPC treatment.
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language English
publishDate 2025-01-01
publisher American Association for the Advancement of Science (AAAS)
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spelling doaj-art-0f8796be7e6c4d3fad154dc2171aea3f2025-08-20T03:16:04ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0791New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to ClinicMaoping Cai0Fengtao Zheng1Yang-Zi Ren2Chuqian Zhen3Dujiang Fu4Xian-Lu Song5Qing Li6Yuanyuan Qu7Zhe-Sheng Chen8Shan-Chao Zhao9Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510630, Guangdong, PR China.Shantou University Medical College, Shantou 515041, Guangdong, PR China.Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, PR China.Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430072, China.Department of Radiotherapy, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, Guangdong, PR China.Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510630, Guangdong, PR China.Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, New York, NY 11439, USA.Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510630, Guangdong, PR China.Neuroendocrine prostate cancer (NEPC), an aggressive and highly malignant subtype of castration-resistant prostate cancer (CRPC), arises through drug resistance mechanisms involving genomic alterations, epigenetic remodeling, tumor microenvironment (TME) reprogramming, and lineage plasticity. A hallmark of NEPC is its independence from the androgen receptor (AR) pathway, evidenced by diminished or absent AR expression—a key barrier to effective clinical management. Therefore, a comprehensive understanding of NEPC pathogenesis and progression is essential, as it facilitates the identification of potential therapeutic targets and the development of more effective therapies. In this review, we summarize the typical characteristics of NEPC and describe its clinical diagnosis, relevant imaging modalities, current treatment strategies, and associated therapeutic difficulties. We also highlight the core events driving NEPC formation. Furthermore, we discuss potential therapeutic targets for the disease and review pharmacological agents that have demonstrated efficacy against NEPC, aiming to offer innovative perspectives and potential research directions for future NEPC treatment.https://spj.science.org/doi/10.34133/research.0791
spellingShingle Maoping Cai
Fengtao Zheng
Yang-Zi Ren
Chuqian Zhen
Dujiang Fu
Xian-Lu Song
Qing Li
Yuanyuan Qu
Zhe-Sheng Chen
Shan-Chao Zhao
New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
Research
title New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
title_full New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
title_fullStr New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
title_full_unstemmed New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
title_short New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic
title_sort new insights into potential therapeutic targets for neuroendocrine prostate cancer from bench to clinic
url https://spj.science.org/doi/10.34133/research.0791
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