Looking beyond Androgen Receptor Signaling in the Treatment of Advanced Prostate Cancer

Figure 1

Summary of relevant work. In ADPC, androgen-stimulated AR activity drives gene expression profiles related to metabolism and androgen/AR regulates G1/S phase cell cycle progression. In both ADPC and CRPC, the pioneer factor GATA2 contributes to androgen-responsive gene expression via three mechanisms of action: regulating AR expression, promoting activation and accessibility of AR target gene regulatory elements, and aiding in the formation/maintenance of basal chromatin loops between AR target genes enhancers and promoters. In CRPC, Akt and ERK activity leads to MED1 phosphorylation/activation resulting in enhanced locus looping and expression of UBE2C in AR+ and AR− cell contexts. Finally, FoxA1 serves as a master cell cycle regulator in CRPC by facilitating AR-mediated expression of G2/M phase cell cycle genes and through a non-AR-associated role in driving G1/S phase progression.