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 This week we profile a recent publication in Molecular Cancer Therapeutics from Dr. Aimee Laporte (left)
and Dr. Torsten Nielsen (right) at the Vancouver Coastal Health Research Institute.

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

We are studying a group of sarcomas — cancers of the musculoskeletal system — which typically affect adolescents and young adults. Terry Fox would be the most well known Canadian who developed this category of cancer, and for his specific type (osteosarcoma) cure rates have improved from <20% to almost 80% thanks to advances in treatment. However, there are several other types of sarcoma where there hasn’t been as much research and cure rates are not as high. One of the more common, synovial sarcoma, is a focus of research in my lab.

What is the significance of the findings in this publication?

In synovial sarcoma, there is a known oncogene, SS18-SSX, but we have no drugs that target it directly. We have found that SS18-SSX acts by changing the epigenome, and it does so by hijacking and redirecting the activity of enzymes that modify histones. We found that a histone deacetylase inhibitor, quisinostat, is able to reverse some of the oncogenes changes, break up the abnormal complexes it forms, and kills synovial sarcoma cells in vitro and in a new mouse model.

What are the next steps for this research? 

We actually have a clinical trial protocol written up and are trying to get a Canada-wide trial off the ground, in my role as co-chair of the Canadian Cancer Trials Group’s Sarcoma Disease Site Committee. Since histone deacetylase inhibitors may not work well enough as single agents, we are taking a cue from myeloma research and combining them with proteasome inhibitors, with which they have a synergistic effect. We are also involved in preclinical studies and an active trial assessing a new class of epigenomic drugs called EZH2 inhibitors.

This research was funded by:

Canadian Cancer Society Research Institute; Liddy Shriver Sarcoma Initiative; Canadian Sarcoma Cancer Foundation

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