The epigenetic and transcriptional landscape of neuroendocrine prostate cancer

Alastair Davies, Amina Zoubeidi, Luke A. Selth

    Research output: Contribution to journalReview articlepeer-review

    54 Citations (Scopus)


    Tumours adapt to increasingly potent targeted therapies by transitioning to alternative lineage states. In prostate cancer, the widespread clinical application of androgen receptor (AR) pathway inhibitors has led to the insurgence of tumours relapsing with a neuroendocrine phenotype, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests that this lineage reprogramming is driven largely by dysregulation of the epigenome and transcriptional networks. Indeed, aberrant DNA methylation patterning and altered expression of epigenetic modifiers, such as EZH2, transcription factors, and RNA-modifying factors, are hallmarks of NEPC tumours. In this review, we explore the nature of the epigenetic and transcriptional landscape as prostate cancer cells lose their AR-imposed identity and transition to the neuroendocrine lineage. Beyond addressing the mechanisms underlying epithelial-to-neuroendocrine lineage reprogramming, we discuss how oncogenic signaling and metabolic shifts fuel epigenetic/ transcriptional changes as well as the current state of epigenetic therapies for NEPC.

    Original languageEnglish
    Pages (from-to)R35-R50
    Number of pages16
    JournalEndocrine-Related Cancer
    Issue number2
    Publication statusPublished - Feb 2020


    • Androgen receptor
    • DNA methylation
    • Epigenetics
    • Lineage plasticity
    • Prostate cancer
    • Transcription factor


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