I focus on the mechanisms underlying metastatic prostate cancer and resistance to androgen deprivation therapy (ADT).
Our laboratory is focused on steroid metabolism and androgen receptor (AR) function as it relates to prostate cancer. The first line of therapy for metastatic prostate cancer is androgen deprivation therapy (ADT), which blocks the release of gonadal testosterone and suppresses intratumoral concentrations of the most potent androgen, dihydrotestosterone (DHT). However, metastatic disease eventually becomes resistant to ADT. Prostate cancer that progresses in the face of ADT is termed castration-resistant prostate cancer (CRPC) and is frequently driven by tumors acquiring the capability of making their own DHT. We study how this process occurs. Our most important discoveries include identification of the first mutation in the androgen synthesis machinery that is responsible for increasing DHT synthesis in CRPC and demonstration that DHT synthesis in patients with CRPC follows a pathway that circumvents testosterone. We are currently applying these findings to the study of CRPC as it occurs in patients.