Combined BET bromodomain and DNMT inhibition targets critical survival pathways in transdifferentiated prostate cancer.
Lineage plasticity, or transdifferentiation, is increasingly recognized as a resistance mechanism to androgen receptor (AR) inhibition in prostate cancer. Lineage plasticity is characterized by loss of AR signaling and epithelial differentiation, along with activation of stemness-associated pathways, epithelial-mesenchymal transition (EMT), or alternative differentiation programs such as neuroendocrine prostate cancer (NEPC).