Cancer, by its very nature, is enormously challenging to treat. But when a cancer tumor develops a resistance to its treatment that was once successful, it makes the process even more difficult.
Treatment-resistant prostate cancer has posed many intimidating obstacles, but Dr. Nima Sharifi of the Cleveland Clinic has been engaged in a study to help overcome those obstacles. Sharifi shared with HealthScene Ohio some of his current research.
HealthScene Ohio: How common is it for prostate cancer to develop resistance to treatment?
Dr. Nima Sharifi: Each year, an estimated 25,000 men will find out their prostate cancer has changed enough to become resistant to standard androgen-deprivation therapy, also called hormone therapy. At this point, the cancer is still able to thrive despite up-front hormone treatment. It’s a variable time table: In some patients, hormone therapy may slow disease progression for more than a decade; in others, it may keep cancer in check only for a few months. Eventually, prostate cancer cells begin to resist the treatment.
HSO: Why do treatments become ineffective over time?
NS: Anti-androgens are potent drugs that work by cutting off the prostate tumor’s supply of male hormones, which fuel prostate cancer. The drugs have been shown to improve survival in men with metastatic disease. Unfortunately, prostate tumors eventually become resistant to these drugs, and the tumors themselves can start producing the very hormones we try to block.
HSO: What do you hope to accomplish with theTell us about the study you’re undertaking on therapy for treatment-resistant prostate cancer.?
NS: 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 U.S. There are few therapeutic options for men whose cancer has become resistant to all therapies. We hope to find ways to improve the uses and roles of current therapies while creating new, longer-lasting, more effective treatments.
HSO: How does prostate cancer become treatment-resistant?
NS: Prostate cancer initially responds to androgen deprivation therapy. However, tumors eventually become resistant because they make their own androgens and thus stimulate androgen signaling pathways.
HSO: What additional challenges do these circumstances pose?
NS: Once tumors become resistant, we need to use treatment strategies that block alternative androgen pathways. There are other treatments such as chemotherapy as well.
HSO: What are some of the problems with existing treatments for prostate cancer, which you hope your research will help solve?
NS: New drugs and a clearer understanding of how the body reacts to them are both urgently required to improve outcomes for treatment-resistant advanced prostate cancer. This work provides an important foundation that hopefully will lead to better treatment strategies for this disease.
HSO: How do you expect your study to improve treatment of treatment-resistant cancers?
NS: In our recently- published study, we showed for the first time how a class of advanced prostate cancer drugs is processed in the body and how their anti-tumor activity might change depending on how they are metabolized. These findings, just published in Cell Chemical Biology, may lay the foundation for improving therapies for treatment-resistant, aggressive prostate cancer.
HSO: What are some of the problems with existing treatments for prostate cancer, which you hope your study will help solve?
NS: New agents and a clearer understanding of drug mechanisms are both urgently required to improve outcomes for treatment-resistant advanced prostate cancer. This work provides an important foundation that hopefully will lead to better treatment strategies for this disease.
HSO: How common is it for prostate cancer to develop resistance to treatment? Is there a general time table on which that change might occur, or does it vary widely?
NS: Each year, an estimated 25,000 men will find out their prostate cancer has changed enough to become resistant to standard androgen-deprivation therapy, also called hormone therapy. At this point, the cancer is classified as castration-resistant prostate cancer, meaning that the cancer is still able to thrive despite up-front hormone treatment. It’s a variable time table: In some patients, hormone therapy may slow disease progression for more than a decade; in others, it may keep cancer in check only for a few months. Eventually, prostate cancer cells begin to resist the treatment.
HSO: How does the success of conventional therapies diminish as prostate cancers become resistant? How quickly does the effectiveness drop off?
NS: Next-generation anti-androgens are potent drugs that work by cutting off the prostate tumor’s supply of androgens (male hormones), which fuel prostate cancer. The drugs, used in patients whose cancer has become resistant to hormone deprivation therapy, have been shown to improve survival in men with metastatic disease. Unfortunately, prostate tumors eventually become resistant to these drugs, highlighting the need for new therapies.
HSO: What sort of success rate have you seen thus far with the therapies utilized in your study?
NS: Our team’s new findings suggest that effective steroidal anti-androgens share common metabolic activities and that their metabolites should be closely examined for their effects on tumor survival. The findings may also guide medical decision making in the use of steroidal vs. non-steroidal drugs for advanced prostate cancer.
HSO: With the findings of your study now published, what are the next steps as you continue work to develop treatment alternatives?
NS: These findings must be considered for the development of better treatment strategies. Our goal is to improve the use and role of these existing drugs and, hopefully, design new therapies that work better and longer.
Jenny Wise is a contributing writer. Feedback welcome at feedback@cityscenemediagroup.com.
About the Expert
Nima Sharifi, MD is a medical oncologist in the cancer biology department of the Cleveland Clinic Main Campus, where he serves as the Kendrick Family Endowed Chair for Prostate Cancer Research. He received his undergraduate degree in biology from Virginia Polytechnic Institute and State University, and a hisdecorate medical degree from the University of Pittsburgh School of Medicine. He completed a residency in internal medicine at Yale-New Haven Hospital in Connecticut and a fellowship in medical oncology at the National Cancer Institute in Maryland. Dr. Sharifi has been honored by such organizations as the American Cancer Society, National Cancer Institute, American Society for Clinical Investigation and American Association for Cancer Research.
