Cover Picture: Castration resistant prostate cancer (CRPC) is an aggressive and therapy-resistant state of prostate cancer with metastasis spreading and high mortality. The figure illustrates the mechanisms identified so far leading to the emergence of resistance to androgen deprivation and androgen receptor (AR)-targeted therapies. CRPC adapts to AR signaling deprivation by restoring the nuclear receptor signaling through genomic rearrangements and mutations in the AR locus or its cofactors. Alternatively, tumor cells transition toward an AR-independent lineage with neuroendocrine features. CRPC showing neither activation of the AR program nor neuroendocrine markers (DNPCs, double negative prostate cancer) are characterized by activation of the FGFR-MAPK pathway. A gastrointestinal (GI) circuit and the WNT pathway were also identified in CRPC to support tumor growth following AR signaling impairment.
view this paper