completed projects are presented in my .
In 2023, we secured a highly competitive 5 year operating grant
from the Canadian
Institutes for Health Research to continue our research
program in synovial sarcoma . My group
will be characterizing the enhancer landscape in synovial sarcoma
(collaborating with Martin Hirst, to develop novel technologies
for detection of enhancer-RNAs), and working with Michael
Underhill to characterize and apply a mouse model for synovial
sarcoma to investigate epigenetic treatment strategies (with a
view towards supporting clinical trials through the International
Rare Cancers Initiative).
This major program project was funded by the US National Institutes of Health through their FusOnC2 (Fusion Oncoproteins in Childhood Cancer) program. Working with collaborators at the University of Utah, Memorial Sloan-Kettering Cancer Center in New York, and Deutsches Krebsforschungszentrum we are undertaking a comprehensive program to develop conditional models probing the origins of synovial sarcoma, to determine how its mutant oncoprotein alters the epigenomic landscape of mesenchymal tissues, and to identify therapeutic vulnerabilities. Within this consortium, I direct the clinical specimen and translation core.
The Terry Fox Marathon of Hope represents a national initiative to accelerate Canada's transition to a future of precision oncology -- treatment directed to the specific underlying molecular mechanisms driving each individuals' tumor biology. Our group has, in collaboration with prominent sarcoma researchers at the University of Toronto, been funded to generate a public resource of genomic, transcriptomic, epigenetic, histologic and clinical information about sarcomas. We are currently focussing on synovial sarcoma, chondrosarcoma and a spine tumor type called chordoma.
Gregg Morin, Yueyang Li, Stephen Chia, Sam Leung, Julie Ho, Shelby Thornton, Jamie Yu, Elahe Shenasa, Torsten Nielsen. Development of novel breast cancer biomarkers.
We have been funded by the Canadian
Cancer Society to work with Gregg Morin's recently-developed
SP3-CTP proteomics technology: developing proteomics-based
profiles on pathology biopsy specimens and validating their use as
potential clinical tests. We have been awarded additional funding
from the Canada Foundation
for Innovation to identify, source and install new
technologies for in situ validation of cancer biomarkers. With
these funds, we have obtained a nanoString Digital Spatial
Profiler, Leica autostainers, Aperio ScanScope and Zeiss Axioscan
hardware and associated image analysis software that actively are
being implemented for this program of research.
Beginning with some of the first molecular profile work in breast cancer, our group has been developing practical clinical tests for the major molecular subtypes of breast cancer, tests that can determine biology, guide risk assessment and therapy. This has led to some of my most cited papers which have related to development of immunohistochemical panels for Luminal and Basal subtypes, and the PAM50 gene expression profile. The latter was transferred to the nanoString platform and has been cleared for use by the FDA, Health Canada and EU as a validated clinical test known as Prosigna. Ongoing work seeks to extend these findings – better IHC panels, identification of additional low risk groups who can safely undergo therapeutic de-escalation, and predictive tests.
Torsten Nielsen, Sam Leung, Zuzana Kos, David Rimm, Lisa McShane,
Mitch Dowsett, Dan Hayes. International Ki67 in Breast Cancer
Working Group.
The proliferation marker Ki67 is convenient, inexpensive, technically & biologically sensitive and specific and can be used to differentiate low risk breast cancers that need limited treatment beyond surgery from high risk cases that need more aggressive treatment. However, as we have detailed over a decade of research, precise and accurate scoring of the Ki67 proliferative index is challenging. We are continuing to support pathologists worldwide in delivering this biomarker through development and dissemination of supporting software and guidelines for visual and digital scoring.
Torsten Nielsen, Elahe Shenasa, Katherine Rich, Ali Bashashati. Optimizing
triple negative breast cancer therapy based on immune cell
morphology.
In our grant funded by The
Cancer Research Society we are using digital image analysis
technology being developed by biomedical engineering collagues to
assess immune infiltrates that, within a
clinically high-risk but molecularly heterogeneous group of
breast cancers, may (a) have such a good prognosis that
chemotherapy may not be needed, or (b) benefit specifically from
capecitabine treatment as opposed to conventional chemotherapy,
checkpoint or PARP inhibitors.