Figure 4.

Hypothetical model of disparate actions of AR signaling: Canonical AR cistrome drives expression of genes associated with differentiation and luminal cell identity. This phenotype is highly sensitive to anti androgen therapies, as such PCa patients that display canonical AR signaling are highly responsive to AR targeted therapies and have prolonged survival. AR gene mutation, alternative splicing, protein modifications, altered level of AR co-factors and in response to androgen ablation therapies, non-canonical AR cistrome emerges which drives expression of genes associated with deregulated cell cycle, metastasis, lineage plasticity. Such changes result in androgen independent growth and proliferation in PCa and drive castration resistance. Research efforts aimed at developing therapeutic interventions that help restore canonical AR cistrome in CRPC are warranted.