The longer medicine's war with prostate cancer drags on, the smarter the enemy is becoming. Like any nemesis worthy of the name, prostate cancer is learning to evolve and adapt defenses against even some of our most powerful weapons.
Case in point: Among the most potent attacks in our arsenal are anti-androgens. These drugs work by cutting off the prostate tumor's supply of male hormones, such as testosterone, which fuel prostate cancer. But the tumors eventually and inevitably become resistant to these drugs.
Now some scientists at the Cleveland Clinic may have just tipped the arms race in our favor. Their research into how galeterone, a steroidal anti-androgen, is processed in the body is laying the foundation for improving therapies for treatment-resistant, aggressive prostate cancer.
"Despite an array of improved treatment options that have become available over the past decade, prostate cancer remains the second leading cause of cancer mortality in men in the United States. There are few therapeutic options for men whose cancer has become resistant to all therapies," said Nima Sharifi, MD, lead author on the study. "Our goal is to improve the use and role of these existing drugs and hopefully design new therapies that work better and longer."
Sharifi's team learned that when galeterone is metabolized, it is converted to an intermediate molecule which blocks androgen synthesis and reduces the amount of androgens available to cancer cells. One pitfall is that galeterone is also converted to another molecule that may stimulate the tumor.
The research team's data suggest that effective steroidal anti-androgens share common metabolic activities. In turn, these metabolites need to be closely examined for their effects on tumor survival. The data may also likely inform medical decision making in the use of steroidal versus non-steroidal drugs for advanced prostate cancer.
This is not Sharifi'a first time into the breach. His previous research likewise found that another steroidal anti-androgen drug, abiraterone, is metabolized in a similar manner.
"New agents and a clearer understanding of drug mechanisms are both urgently required to improve outcomes for treatment-resistant advanced prostate cancer," said Dr. Sharifi. "This work provides an important foundation that hopefully will lead to better treatment strategies for this disease."
The research has been published in the journal Cell Chemical Biology.