Biomarker-Based Targeting of the Androgen-Androgen Receptor Axis in Advanced Prostate Cancer

Figure 1

The androgen-AR axis. Testicular testosterone (T) production is regulated by the hypothalamic-pituitary axis of the endocrine system. In prostate cancer cells, T is rapidly converted to dihydrotestosterone (DHT) by 5 α-reductase (5α-R) enzyme activity. The AR gene is composed of 8 exons, with exon 1 encoding the N-terminal TAU1 and TAU5 transcriptional activation domains, exons 2 and 3 encoding the AR DBD, and exons 4–8 encoding the AR hinge (h) region and COOH-terminal LBD and AF-2 domains. DHT binding to mature AR protein induces nuclear translocation. Active AR binds target genes and recruits coregulatory proteins and components of the basal transcriptional machinery to achieve transcriptional activation. Abbreviations are defined in the text.