fig3

Figure 3. Mechanisms of drug resistance to androgen receptor signaling inhibitors (ARSI). Following uptake of DHEA-SO₄ into the prostate by SLCO transporters a number of enzymes with either increased expression or germline mutations that result in increased activity/stability may contribute to ARSI drug therapy resistance (shown in green); similarly, a number of enzymes with either decreased activity or germline mutations that decrease activity/stability may contribute to drug resistance (shown in red). AKR1C3 may be an exception in that it is highly upregulated by androgen deprivation, and nsSNPs in conserved positions may reduce its activity. All enzymes are listed in italics by their gene names as described in the legends to Figures 1 and 2