Reversing-or Rewiring-Lineage Plasticity? Lessons from EZH2 Loss in Prostate Cancer - PubMed
5 days ago
- #EZH2
- #Prostate Cancer
- #Lineage Plasticity
- EZH2 inhibitors were proposed to counteract lineage plasticity (LP) in prostate cancer and resensitize tumors to androgen receptor (AR) inhibition.
- Genetic deletion of Ezh2 in a mouse model did not reverse LP but promoted neuroendocrine (NE) differentiation via KLF transcription factor family activation.
- EZH2 loss altered the AR chromatin-binding landscape, redirecting it toward KLF-associated genomic sites.
- The study suggests EZH2 loss rewires transcriptional networks and reshapes the AR cistrome rather than simply reversing LP.
- Findings are relevant to ongoing clinical trials testing EZH2 inhibitors in metastatic prostate cancer, emphasizing the need to define optimal therapeutic contexts.