University of Pittsburgh Cancer Institute (UPCI)


Androgen Action

Androgen Androgens are intimately associated with prostate cancer genesis and progression, and androgen deprivation therapy remains the most effective and standard treatment for patients with metastatic prostate cancer. Unfortunately, androgen deprivation therapy is not curative and the patients eventually relapse with castration-resistant prostate cancer, which is responsible for the death of most prostate cancer patients. Elucidating the mechanism of prostate cancer progression toward castration-resistance status, including the role of androgens and androgen receptor, remains a major challenge in prostate cancer research. Thus, a major focus of the PCP is to investigate basic mechanisms of androgen action, with a goal of identifying novel and effective therapeutic targets for castration-resistant prostate cancer.

Selected Publications

  • Intermittent androgen deprivation therapy (IADT) was developed to improve the quality of life and retard prostate cancer progression to androgen resistance. IADT involves regrowth of the tumor during the off-cycle upon testosterone recovery. Finasteride administration in IADT can improve survival of mice bearing prostate tumors when the duration of the off-cycle in IADT was fixed. However, maximum possible lengthening of the off-cycle by 5alpha-reductase inhibition is not associated with survival improvement of the animals (Wang Y, et.al., Prostate. 70:147-54, 2010).
  • Inhibition of 5alpha-reductase during prostate tumor regrowth in mice enhances the expression of U19/Eaf2, an androgen-regulated tumor suppressor, and suggests that off cycle 5alpha-reductase inhibition may enhance the efficacy of IADT. (Gupta S. et. al., Prostate. 70:1575-85, 2010).

Members

DeFranco, Donald, PhD
Pharmacology & Chemical Biology 		Luo, Jianhua, MD, PhD
Pathology
Dhir, Rajiv, MD
Pathology		 Nelson, Joel, MD
Urology
Gingrich, Jeffrey, MD
Urology		 Wang, Zhou, PhD
Urology
Li, Song, MD, PhD
Pharmaceutical Sciences