Figure 3.

Alterations in glucocorticoid receptor pathway as a mechanism of enzalutamide resistance. Enzalutamide inhibits binding of androgens to the AR, suppressing transcription of AR-regulated genes and therefore suppressing prostate tumor growth (top). The GR regulates an overlapping but not identical set of genes as AR, therefore activating a subset of the AR-regulated genes. Increased GR expression, along with downregulation of enzyme 11β-hydroxysteroid dehydrogenase-2 that converts GR agonist cortisol to the inactive metabolite cortisone, can lead to increased transcription of this subset of AR-regulated genes and restoration of tumor growth (bottom). Created with Biorender.com.