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Publications of the Week

Divergent Biological Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

By October 1, 2018No Comments

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 This week we profile a recent publication in Clinical Cancer Research from
Dr. Peter Black (pictured) at the Vancouver Prostate Centre.

Can you provide a brief overview of your lab’s current research focus?

My research program at the Vancouver Prostate Centre has focused on the advancement of precision therapy for bladder cancer, including translational research into novel biomarkers and targeted therapies. We are studying the genomic and transcriptomic landscape of muscle invasive bladder cancer before and after chemotherapy in an effort to identify markers of response and pathways of resistance. We have developed and commercialized a single patient transcriptomic classifier that predicts response to chemotherapy based on molecular subtypes. We have specifically honed in on Notch signaling and were the first to describe the oncogenic role of Notch2 in bladder cancer. We continue to characterize the signaling pathways that distinguish the Notch2 effects from the tumour suppressor role of Notch1.

What is the significance of the findings in this publication?

Molecular subtyping has become a major concept to classify bladder cancer. For example, there is a lot of interest to use it to predict response to novel immunotherapies. Our work shows that treatment affects not only the subtype of a tumour, but also the validity of current subtyping models (there are at least 5 different ways to subtype). We show that you cannot simply take the current models and apply them to tumours post-chemo. This has direct implications for the immunotherapy space where subtyping has been done with no regard to timing of chemo. More importantly, the work shows the shifting biology in tumours resistant to chemo. It provides some hypotheses for which treatment might be best next line in individual patients.

What are the next steps for this research?

We want to delve more into mechanisms of resistance and finding ways to overcome resistance. So we want to determine what is really different (what is gained and what is lost) in the resistant tumours. We are also integrating this with whole exome sequencing and proteomic from the same cohort.

This research was funded by:

This was done in close collaboration with GenomeDx Biosciences, so they actually funded the transcriptomics.

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