Sarcoma

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).

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, with additional work planned on clear cell sarcoma and myxoid  liposarcoma.

Early in my career, working with Matt van de Rijn, and Stanford-UBC collaboration identified macrophage colony stimulating factor rearrangements and overactivity as the driver event in TGCT, a neoplasm that destroys joints in young people. This led to others developing CSF1R inhibitors as a new treatment for this disease, one of ASCO's advances of the year in 2019. Recent work from our groups have reopened questions into cooperating mutations and where and how CSF1 is expressed, the answers to which we believe will guide optimal use of these new treatments. Supported by a Terry Fox Research Institute Program Project in collaboration with David Huntsman, we've recently re-opened our TGCT research program and our collaborations with Stanford and Leiden.

Supported by the friends and family of Josh Lombardi, including through the BC Cancer Foundation Tour de Cure, we have opened a dedicated research program in DSRCT, a dangerous form of sarcoma that arises in the abdominal cavity of young adults. Having surveyed the literature, what others are doing and what the needs are, we have decided that one thing the field really needs is a conditional mouse model that can be used to develop much-needed new therapies.

Breast Cancer

Gregg Morin, Yueyang Li, Stephen Chia, Sam Leung, Christine Chow, Gian Negri, Seti Boroomand, 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.