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SIU 2017

SIU 207: SIU-ICUD Joint Consultation on Bladder Cancer - Basic Science

Lisbon, Portugal (UroToday.com)  This is a new chapter not previously included in the 2012 version. Dr. McConkey went through the data very quickly, but highlighted the areas of focus in the chapter. Importantly, he was very blunt that they do not yet have enough data to make guideline recommendations, but they may be close. There has been a lot of development in understanding the genomic makeup of bladder cancer in the past few years. The chapter is split into the update on the following major topics (along with some select highlights from recent results).

  1. Development Mechanics
  2. Animal Models
  3. Mutations and Mechanisms
  4. DNA Damage and Repair
  5. Receptor tyrosine kinases
  6. Immunotherapy
  7. Epigenetics
  8. Molecular expression subtypes
  9. Non-coding RNA
  10. Metabolomics
  11. Cancer stem cells
  12. Metastases
  13. Liquid biopsies
An overarching theme of the multiple sections is the growing evidence of different genomic profiles that can separate bladder cancer into further subcategories. These, as previously described, include the basal subtype, the luminal subtype, and the p53-like subtype. These, or similar separation, has been seen in multiple well known recent publications by MD Anderson, Lund, UNC and the TCGA dataset. This has implications for not only diagnosis, but also treatment, as the subtype may predict treatment response. However, while these are promising, they are not yet robust enough to be incorportated into the guidelines.

DNA damage response (DDR) gene mutations in UC was another important focus in BCa, and all cancers in general. DDR gene mutations (ie BRCA 1/2, ATM, ERCC2) leads to microsatellite instability (MSI) and higher level of neoantigens. Their presence has been associated with response to therapy as well, specifically chemotherapy. Immunotherapy also depends on higher levels of tumor mutational burden (TMB), which bladder cancer is known to have a high neoantigen load.

He and his working group helped consolidate all this novel data into the first edition of the chapter of “Basic Science” for bladder cancer. His main conclusions were as follows:
  1. Bladder cancers can be grouped into basal and luminal molecular subtypes characterized by biomarkers associated with normal urothelial development. The molecular subtypes are clinically significant.
  2. Bladder cancer mutational profiles are associated with chemotherapy response.
  3. Better preclinical tools are being developed to help define the molecular mechanisms involved in tumor progression and metastases.
  4. Chromatin modifiers, non-coding RNAs, and metabolism are all biologically significant – not yet clear how they are clinically significant.
  5. “Liquid biopsies” have the potential to reveal tumor genomic properties.

Presented by: David McConkey 

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal