3D chromatin dynamics in cellular neuroendocrine transformation

Lineage plasticity enables cancer cells to bypass therapeutic pressure, but the underlying chromatin mechanisms remain incompletely defined. A recent study by Lu et al. uncovers how the transcription factors NKX2-1 and FOXA2 reprogram 3D genome architecture to activate neuroendocrine gene networks during the transition from castration-resistant prostate cancer (CRPC) to neuroendocrine prostate cancer (NEPC) (Lu et al., 2025). Importantly, pharmacological inhibition of CBP/p300 markedly suppresses NEPC growth in vitro and in vivo, revealing a promising therapeutic avenue for advanced disease. These findings illuminate how spatial chromatin reorganization can drive cell fate transitions, positioning 3D genome dynamics as a key determinant of cellular identity in both development and disease.