Changing Landscape of Prostate Cancer Research and Development

25 Years of Prostate Cancer Treatments - Some Thoughts from ASCO

By Marco Gottardis, Janssen Oncology, Prostate Cancer DAS Leader

As I attend my 19th ASCO annual meeting this year, I take a minute to pause and think about how treatments in various cancers have evolved in the past few decades. Some approaches have stumbled, while others have raced forward showing great promise and changing positively the lives of thousands of cancer patients.  I have seen great strides overall in cancer where individuals with cancer can continue to live active, fulfilling lives. 

As the head of the Prostate Cancer Disease Area Stronghold at Janssen Oncology, I have the amazing opportunity to work alongside brilliant and passionate scientists in this area.  I get a ringside seat on the enormous changes taking place in this disease.

In all things research, finding answers for the treatment of prostate cancer has been a slow and arduous process. When I first started my career in cancer research, 25 plus years  ago, there was little available for prostate cancer; it was a virtual desert.  Surgical castration, for which Charles Huggins received his Nobel prize >50 years ago to cut off the flow of testosterone that fuels the prostate cancer, was the only real treatment. While surgery was not a welcomed alternative, it was an option. It provided hope and time, albeit mostly short-lived, in outcomes for metastatic prostate cancer patients. In the late 1970’s, there was the emergence of luteinizing-hormone-releasing hormone (LHRH) agonists. Sadly, despite the positive side of not needing castration surgery, this approach gave similar outcomes.  There was no benefit to overall survival and after that treatment ran its course and was no longer effective, there was no plan B.

Since then, it is clear that the landscape of prostate cancer has changed by the expanding approval of new agents with new or improved mechanisms of action. Research has driven approaches that include the ability to inhibit synthesis of androgens and androgen receptor (AR) antagonists that more effectively directly block AR–a major break-through for those in the advanced stages of the disease. These new agents, for the first time, show evidence of an increase in overall survival in prostate cancer patients. We’ve moved forward, but for men facing prostate cancer, not enough.

We continue to need treatments that can directly prevent the growth of prostate cancer, and we need options for treatment without the ill effects of testosterone deprivation. We also need answers for earlier stages of disease, and in prevention to stop the cancer from developing in the first place.

In my opinion, for that to happen, we need to work on the following strategies:

One, provide another alternative for patients who have failed all hormonal therapies. These treatments will include third-generation AR agents, that can block the androgen receptor through other mechanisms than just blocking at the androgen binding site or androgen synthesis.

Two, develop greater understanding of prostate cancer molecular phenotypes to enable personalized targeted treatment regimens.  As our molecular understanding of prostate cancer grows, so does our ability to identify gene defects and mutations to enable selection of personalized targeted therapies for patients. One such example is the class of drugs referred to as poly ADP ribose polymerase (PARP) inhibitors, which prevent cancer cells from repairing their DNA and eventually causing them to die. It’s a new mechanism for treating prostate cancer, appropriate for certain patients, with DNA repair defects. A subgroup of 20-25 percent of prostate cancer patients have DNA defects which in the future will be identified by a simple blood test.  Initial clinical data suggests that prospective selection of patients with DNA repair defects can predict response to PARP inhibitors.

Three, treat patients earlier, to see if we can provide more durable responses in earlier stages of the disease and to drive cures. A new generation of treatments that include vaccines, targeted therapy, immune-therapy and AR inhibitors may have the opportunity to become the anchor therapies for these earlier stage patients.

If I think about the progress being made for prostate cancer treatment, I am pleased to say now, some two decades later that the sand is shrinking and our hopes are becoming less distant mirages. Prostate cancer remains a cancer that affects large numbers of patients. It remains a tumor that has not been completely solved and the biology is just being fully understood. With all our scientists working hard to make a difference, there are numerous promising opportunities to provide new types of therapeutics that will change the course of this disease.