North Texas
2:20 pm
Mon August 15, 2011

New Pathway To Potential Therapies For Advanced Prostate Cancer

Dallas, TX –

Of about 220,000 men in the U.S. diagnosed with prostate cancer each year, 32,000 will develop an advanced, incurable form of the disease. The standard treatment is hormonal therapy - removing testosterone believed to accelerate the growth of tumors. It often works - usually, though, for a short time. But researchers at University of Texas Southwestern Medical Center have learned more about what stimulates growth of the tumors. They call it a new pathway to potential drug therapies for advanced prostate cancer. In KERA's weekly Focus on Health, Sam Baker talked with Dr. Nima Sharifi. He's an Assistant Professor of Internal Medicine and the senior author of the study about the new pathway.

Dr. Sharifi: Since this is a hormone or androgen-driven disease, what we generally do is that we take away testosterone or androgens. And that therapy usually works really well, initially, but it's almost always temporary. And this observation that's been around for mostly 30 years and has been studied in much greater depth the past seven or eight years, is that if you take those pieces of tissues that are now resistant to hormonal therapy, you'll see that even though you've taken away androgen or testosterone from the serum, these tumors start making their own androgens. And the general assumption has been that to get to the most potent form of androgen, or what we call DHT (Dihydrotestosterone), it's generally been assumed you have to go through the normal testosterone, the normal physiologic pathway, and that's really where this finding comes in. And that is we know those androgens are there - we've known that for 30 years - but no one's ever studied how they get there. So, you can think of this as a roadmap to getting at the most potent androgen that drives the disease. And until you rigorously define what road the tumor takes to get to that end point, you can't block it.

It really does make a difference in trying to develop drugs that target the right steps in the pathway so that we block that and get an effective therapy.

Sam Baker: So are we talking about a new form of therapy? Are we talking about something that could lead to prolonged life or, perhaps, better quality of life? What is it exactly?

Dr. Sharifi: It's really the hope, but there are really a lot of steps that are between this work and the development of better treatments. It can be done, but we're several years off from that.

Sam: How many years did it take to get to this point?

Dr. Sharifi: Um, well, from the first observation to basically publishing this paper took about three years.

Sam: And how many years can you foresee ahead of you with this?

Dr. Sharifi: In terms of developing a drug, it really depends on the level of interest. You know drug development in cancer has been accelerated over the past ten years, so a lot of it depends on the level of interest that's there out in the scientific and medical community for getting this done.

Sam: There are currently several treatments for advanced prostate cancer. If I found myself being diagnosed with that, what would I have to choose from?

Dr. Sharifi: The initial treatment for advanced prostate cancer is still testosterone deprivation. That really hasn't changed. And because of the finding I mentioned in terms of tumors making their own androgens, there are several lines of hormonal therapies we can do to block that pathway in a different way, that often times you can get responses.

The newest hormonal form of therapy was FDA-approved in April. You know these advances are incremental, but there's no doubt that this drug is very active and does prolong the life of men who have the refractory or the resistant form of prostate cancer.

Sam: Is this the so-called vaccine for advance prostate cancer or something different?

Dr. Sharifi: No, that's something different. What I'm talking about are mainly hormonal therapies. The vaccine therapy or Provenge is FDA-approved and available, but it works through a completely different mechanism.

Sam: Early detection is important. But the first hurdle is just getting men to go to the doctor in the first place.

Dr. Sharifi: I think it's particularly important for men who have a family history of prostate cancer. And it's very complicated because screening is not a very straightforward thing to do. There's no perfect screening method. But for men who have the more aggressive form of prostate cancer, I think if you were able to treat it earlier, you'd have a chance of being able to take it away entirely and potentially curing it.

Dr. Nima Sharifi is an Assistant Professor of Internal Medicine at University of Texas Southwestern Medical Center.

For more information:
http://www.utsouthwestern.edu/utsw/cda/dept353744/files/647521.html