Does glucocorticoid receptor (GR) signaling compensate for androgen receptor (AR)
 function in castration resistant prostate cancer (CRPC)?

This proposal seeks to test the hypothesis that an alternative hormonal receptor, the
glucocorticoid receptor (GR), can compensate for the lack of androgen receptor (AR) activity in prostate cancer to impart resistance to potent hormonal therapies. The experiments proposed include a combination of preclinical cancer modeling, precise molecular biology, bioinformatics, and interrogation of circulating tumor cells from patients with castration resistant prostate cancer (CRPC). Should the hypothesis be supported, this work will challenge existing paradigms regarding glucocorticoid use in CRPC, provide novel therapeutic targets for the disease, and open the door for further mechanistic study of the interaction between the glucocorticoid receptor and androgen receptor in prostate cancer.