ASCO 2017: Expanding the Actionable Landscape: Bladder Cancer Genomics - Introduction

Chicago, IL ( Dr. McConkey gave a most interesting introductory talk to the topic of bladder cancer genomics research. He pointed out the current ongoing genomic revolution in bladder cancer, consisting of completion of large scale genomic projects such as The Cancer Genome Atlas (TCGA), discovery of the basal and luminal subtypes of bladder cancer, extensive research in DNA damage and repair mutations and correlation to neo-antigens and overall mutational burden.

Significant therapeutic benefit from several treatment strategies has already been acquired. This included neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC), intravesical therapy (BCG and chemotherapy) for non-muscle invasive bladder cancer (NMIBC) and the discovery and application of immune check point inhibitors (ICPI) for both MIBC and NMIBC.

According to Dr. McConley, we are now in an era where researchers are trying to comprehend if response to ICPI is predictable. Extensive research is being done to understand the role of immunohistochemistry with anti-PDL1 in tumor tissues versus stoma tissue and the role of T-cell biomarkers. Additionally, associations are being sought to neo-antigen burden and mutational load.

Dr. McConkey concluded his presentation by stating the most intriguing questions to date involving bladder cancer genomics research. These include:

1. Do some bladder cancer patients have inherited (germline) DNA damage response (DDR) mutations?
2. Are DDR mutations associated with benefit from immunotherapy?
3. Does intra-tumoral heterogeneity in DDR mutations affect prognosis and/or benefit from systemic therapy?
4. And finally, are mismatch repair (MMR) defects associated with benefit from immunotherapy in bladder cancer?

Hopefully, these can be answered in the near future and considerably advance the range, quality and sequence of therapies given to bladder cancer patients, resulting in significant clinical benefit.

Presented By: David James McConkey, PhD, Director, John Hopkins Greenberg Bladder Cancer Institute

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA