Lineage plasticity in prostate cancer depends on FGFR and JAK/STAT inflammatory signaling

Background: The inherent plasticity of tumor cells provides a mechanism of resistance to molecularly targeted therapies, exemplified by adeno-to-neuroendocrine lineage transitions in prostate and lung cancer. Here we investigate the root cause of lineage plasticity following Trp53 and Rb1 loss in genetically engineered mouse models, murine and patient-derived organoid cultures, and patient biospecimens with castrate-resistant prostate cancer.