Combination Therapy With Testosterone and Statins to Inhibit Tumor Cell Proliferation in Castration-Resistant Prostate Cancer
Abstract
Androgen receptor (AR) is a critical factor in regulating gene expressions in prostate cancer (PCa) and stimulating tumor growth. Patients with metastatic prostate cancer can be treated with standard androgen deprivation therapies (ADT) including surgical or medical castration in order to suppress AR activity. However, the tumors will eventually develop resistance in a more aggressive stage of cancer (termed castration-resistant prostate cancer, or CRPC) with restored AR activity. Recently, the Food and Drug Administration approved two new drugs to treat CRPC, including abiraterone (CYP17 inhibitor) and enzalutamide (a more potent AR antagonist). The majority of CRPC patients respond initially to these treatments, but most relapse by 1 year through unclear mechanisms. The failure of this more aggressive ADT treatment indicates the need for new treatment strategies. Recent studies suggested AR could also be anti-proliferative in PCa through suppressing DNA synthesis and cell cycle. This provides a rationale for using androgen therapy to treat CRPC and such therapies are currently in clinical trials. However, we speculate that the growth inhibition effect of androgen will be overcome by growth-promoting effect from AR-activated metabolic functions, particularly stimulation of lipid/cholesterol synthesis. Therefore, we are proposing an innovative approach to treat CRPC patients with high dose testosterone in combination with statins (inhibitors of cholesterol synthesis) to suppress tumor cell proliferation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510519
Entities
People
- Changmeng Cai
Organizations
- United States Army
- University of Massachusetts Boston