Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer - PubMed
6 hours ago
- #Chromatin
- #Epigenetics
- #Prostate Cancer
- Treatment-induced neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC).
- t-NEPC is characterized by loss of androgen receptor (AR) activities and gain of neuroendocrine gene expression.
- Incidence of t-NEPC has increased to up to 20% of CRPC cases due to AR pathway inhibitors (ARPi) treatment.
- Epigenetic programs between CRPC and t-NEPC are markedly distinct despite conserved genomic alterations.
- Neuroendocrine transformation (NET) involves changes in DNA methylation, histone modifications, chromatin accessibility, and 3D chromatin organization.
- Key regulators of NET include lineage-specific transcription factors and chromatin modifiers.
- NEPC progression follows a mixed model of clonal selection and transformation.