May 4, 2019 - Dr. Martin Gleave gave the AUA 2019's Ramon Guiteras Lecture, a plenary invited lecture named after the AUA's founder. Click here to read the original story at AUA Daily News, the text of which is copied below.
The adaptive molecular landscape of advanced prostate cancer presents significant treatment challenges, according to Martin E. Gleave, MD, who discussed the progress and future research directions for targeting this molecular landscape during the annual Ramon Guiteras Lecture Saturday morning at AUA2019.
Dr. Gleave is Distinguished Professor and Chairman of the Department of Urologic Sciences at the University of British Columbia (UBC), and is also the founder and Director of the Vancouver Prostate Centre, a UBC and National Centre of Excellence. He has also founded several companies, including OncoGenex Pharmaceuticals, which was named Canadian Biotech Company of the Year in 2010.
Dr. Gleave said targeting the androgen receptor (AR) pathway redefined the treatment landscape for advanced prostate cancer, but researchers are now “starting to see a ceiling effect.” Combining agents such as abiraterone and enzalutamide, or sequencing them, has proven to be ineffective due to development of cross-resistance. There’s a clear need for improved biomarkers to help guide treatment decisions.
“Metastatic tissue biopsies of castration-resistant prostate cancer [CRPC] have helped define the genomic landscape,” he said, but “a single biopsy may actually underestimate or incorrectly identify driver mutations, and hence we need liquid biopsies.”
Dr. Gleave’s research group helped develop a circulating tumor DNA biopsy that has been shown to be highly concordant with tissue biopsies from metastatic sites, while surveying the intra-patient heterogeneity better than a single biopsy from a single site. Using this biopsy, Dr. Gleave and colleagues showed that patients treated with abiraterone in the first-line setting who then crossed over to receive enzalutamide had higher prostate specific antigen response than patients treated in the reverse order.
“Some mechanisms of resistance to abiraterone may allow for subsequent response to enzalutamide, but it’s very unusual in the reverse,” he said. “This is why we need biomarkers.”
Meanwhile, a better understanding of the genomic landscape of advanced prostate cancer has revealed other potential pathways and targets that may also offer treatment options.
“The pace of change is accelerating. We were applied anatomists for 200 years, and over the last century have evolved as applied pathophysiologists,” Dr. Gleave said. “In the next few years we’ll be digitizing biology at a level that will help us better understand, identify and treat our patients at the individual level.”