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Emerging Therapeutic Targets of Neuroendocrine Prostate Cancer

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Abstract

Purpose of Review

Treatment-emergent neuroendocrine prostate cancer (NEPC) is aggressive and lethal. As androgen receptor signaling inhibitors (ARSIs) are increasingly used in earlier disease settings, treatment-emergent NEPC becomes more prevalent, and effective therapies are urgently needed. The purpose of this review was to summarize recent progress on emerging therapeutic targets of NEPC.

Recent Findings

A multitude of therapeutic targets have emerged in NEPC over recent years. These targets may represent drivers of treatment-emergent lineage plasticity or simply be overexpressed on the surface of NEPC cells. Multiple modalities have been employed to drug these targets, with promising preclinical and clinical results.

Summary

Treatment-emergent NEPC represents a distinct and clinically significant subset of castration-resistant prostate cancer (CRPC). Emerging therapeutic approaches have demonstrated encouraging efficacy and safety profiles, offering the potential to improve patient outcomes.

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Data Availability

No datasets were generated or analysed during the current study.

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Funding

XZ received research funding from Conquer Cancer, the ASCO Foundation, the Prostate Cancer Foundation (PCF), and the Department of Defense (DOD) outside of this work. CKCD received research funding from the PCF outside of this work. RRA received research funding from the PCF, the DOD, and the National Cancer Institute outside of this work.

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Authors and Affiliations

  1. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

    Xiaolin Zhu, Chien-Kuang C. Ding & Rahul R. Aggarwal

  2. Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Xiaolin Zhu & Rahul R. Aggarwal

  3. Department of Anatomic Pathology, University of California San Francisco, San Francisco, CA, USA

    Chien-Kuang C. Ding

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  1. Xiaolin Zhu
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  2. Chien-Kuang C. Ding
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  3. Rahul R. Aggarwal
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Contributions

X.Z. wrote the main manuscript text and prepared the figure and the table. R.R.A. oversaw the writing. All authors reviewed and edited the manuscript.

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Correspondence to Rahul R. Aggarwal.

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All reported studies with human subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Competing Interests

RRA is an advisor/consultant for AstraZeneca, Bayer, Bioexcel Therapeutics, Boxer Capital, Clovis, Curio, Dendreon, Exelixis, Janssen, Lumanity, Merck, Novartis, Pfizer, Prostate Cancer Clinical Trials Consortium, and Tersara Consulting; and received institutional research grants/funding from Amgen, AstraZeneca, Janssen, Merck, Novartis, and Zenith Epigenetics.

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Zhu, X., Ding, CK.C. & Aggarwal, R.R. Emerging Therapeutic Targets of Neuroendocrine Prostate Cancer. Curr Oncol Rep 27, 362–374 (2025). https://doi.org/10.1007/s11912-025-01643-9

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