The "Evolution" of Advanced Prostate Cancer Research

Ken Pienta, MD and Director of Research
at the Brady Urological Institute

Prostate cancer affects approximately 230k men per year in the US.  Fortunately, over 90% of men present with localized, treatable prostate cancer.  Unfortunately, approximately 30k men still die of the disease each year in the United States.[1]  Advanced prostate cancer is treated with hormonal therapy, chemotherapy or radiation treatment in combination or alone.  As prostate cancer is a male cancer and driven by testosterone, hormone therapies can shrink and limit the growth of cancer cells.  Chemotherapy and radiation kill rapidly dividing cancer cells -- and have some effect on prostate cancer cells.  In them men who die of prostate cancer, the cancer cells learn or "evolve" to escape these treatments.  

In this blog entry, Ken Pienta, MD and Director of Research at the Brady Urological Institute, discusses how our understanding of advanced prostate cancer has "Evolved" to meet this challenge.  Dr. Pienta was recently awarded a $1.5 million Challenge Award from Prostate Cancer Research Foundation and Movember organizations to investigate circulating tumor cells and disseminated tumor cells in men with metastatic prostate cancer.

"Our understanding of how advanced prostate cancer changes over time is rapidly evolving. Prostate cancer changes over time because it mutates as part of its innate instability of its DNA as well as mutations that develop as the cancer adapts to the therapy to which we subject it (therapeutic pressure). As our understanding of prostate cancer evolution during progression grows, the challenge is to effectively sequence and combine our growing armamentarium of therapeutic agents for maximal patient benefit -- the right drugs, in the right combinations, given at the right time.  

It is especially important to anticipatie the need for therapy before it is clinically apparent; i.e. to move beyond anatomically-based clinical decisions and prognostication to biologically (marker)-driven therapy prediction. Treatment with androgen deprivation therapy (castration therapy, hormonal therapy) inevitably leads to the development of castrate resistant prostate cancer. The second generation anti-androgen (supra-castration) therapies, while effective, are leading to the emergence of new types of prostate cancer. Three phenotypes/genotypes of CRPC after treatment with second-generation agents appear to be increasing in prevalence and remain resistant to treatment: NeuroEndocrine Prostate Cancer (NEPC), Persistent AR – Dependent Prostate Cancer (PADPC), and Androgen Receptor Pathway Independent Prostate Cancer (APIPC). 

It is clear that new treatment paradigms, taking into account cancer cell genetic and epigenetic pathways, contributing factors within the microenvironment, and the macroenvironment of the host / patient need to be developed for this diverse group of diseases."