Related Experiment Video
Updated: Oct 24, 2025
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Current advances of targeting epigenetic modifications in neuroendocrine prostate cancer
Wen-Chi Cheng1, Hung-Jung Wang2,3
1SDGs Teaching and Research Headquarters, Tzu Chi University, Hualien, Taiwan.
Abstract:
Neuroendocrine prostate cancer (NEPC) is the most lethal malignancy of prostate cancer (PCa). Treatment with next-generation androgen receptor (AR) pathway inhibitors (ARPIs) has successfully extended patients' lifespan. However, with the emergence of drug resistance, PCa tumors increasingly adapt to potent ARPI therapies by transitioning to alternative cellular lineage. Such therapy-induced drug resistance is largely driven from the cellular plasticity of PCa cells to alter their phenotypes of AR independence for cell growth and survival. Some of the resistant PCa cells undergo cellular reprogramming to form neuroendocrine phenotypes. Recent evidences suggest that this cellular reprogramming or the lineage plasticity is driven by dysregulation of the epigenome and transcriptional networks. Aberrant DNA methylation and altered expression of epigenetic modifiers, such as enhancer of zeste-homolog 2, transcription factors, histone demethylases, are hallmarks of NEPC. In this review, we discuss the nature of the epigenetic and transcriptional landscapes of PCa cells which lose their AR independence and transition to the neuroendocrine lineage. We also discuss how oncogenic signaling and metabolic reprogramming fuel epigenetic and transcriptional alterations. In addition, the current state of epigenetic therapies for NEPC is addressed.
Insights
Neuroendocrine prostate cancer (NEPC) arises from prostate cancer (PCa) adapting to treatments by changing cell type. Epigenetic and transcriptional changes drive this lineage plasticity, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer (PCa).
- Next-generation androgen receptor pathway inhibitors (ARPIs) improve survival but resistance develops.
- Therapy resistance often involves PCa cells losing AR dependence and undergoing lineage plasticity, including neuroendocrine differentiation.
Purpose of the Study:
- To review the epigenetic and transcriptional landscapes driving PCa lineage plasticity towards NEPC.
- To explore how oncogenic signaling and metabolic reprogramming influence these alterations.
- To discuss current epigenetic therapies for NEPC.
Main Methods:
- Literature review focusing on epigenetic mechanisms and transcriptional networks in NEPC.
- Analysis of studies investigating cellular reprogramming and lineage plasticity in ARPI-resistant PCa.
- Synthesis of current research on epigenetic modifiers and their role in NEPC development.
Main Results:
- Dysregulation of epigenome and transcriptional networks drives NEPC lineage plasticity.
- Aberrant DNA methylation and altered expression of epigenetic modifiers (e.g., EZH2, histone demethylases) are hallmarks of NEPC.
- Oncogenic signaling and metabolic reprogramming contribute to epigenetic and transcriptional changes.
Conclusions:
- Understanding the epigenetic and transcriptional drivers of NEPC is crucial for developing effective treatments.
- Targeting epigenetic modifications represents a promising therapeutic strategy for NEPC.
- Further research into the interplay of signaling, metabolism, and epigenetics is needed for NEPC management.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle