Use of Selective GR Antagonists in Castration-resistant Prostate Cancer

About Use of Selective GR Antagonists in Castration-resistant Prostate Cancer
  • The androgen receptor (AR) is the primary driver of prostate cancer progression and survival and is a successful therapeutic target of many new life-prolonging treatments. However, tumors inevitably develop resistance to AR-targeting therapies and progress to lethal castrate-resistant prostate cancer (CRPC).
  • Increased activity of the glucocorticoid receptor (GR), a protein relative of AR, acts as a mechanism of AR-targeted drug-resistance in some patients by turning on expression of many of the same tumorigenic genes which rescue tumor cells from the loss of AR function.
  • Dr. Conzen and team will determine the efficacy and mechanisms by which several new GR-targeting agents act in combination with AR-targeting therapies to kill prostate cancer cells.
  • Dr. Conzen has initiated clinical trials in CRPC patients to evaluate therapeutic synergy between AR and GR-targeting drugs (enzalutamide and mifepristone, respectively). Using circulating tumor cells from these patients, her team will evaluate whether inhibition of GR activity by mifepristone therapy will predict a therapeutic response in AR-targeted treatment-resistant patients.

What this means for patients: Castrate-resistant prostate cancer (CRPC) is often a lethal disease state in which tumors have developed resistance to AR-targeting therapies. If successful, this project will generate new drugs that inhibit a major mechanism of AR-drug resistance and leverage knowledge of how these drugs work to develop clinical biomarkers of therapeutic response.

Principal Investigator:

Suzanne Conzen, MD (University of Chicago)

Co-investigators:

Geoffrey Greene, PhD, Walter Stadler, MD, Russell Szmulewitz, MD, Diana West, PhD (University of Chicago)