University of Toronto multi-omics projects
To uncover new therapeutic targets and inform more personalized care for chordoma patients, a comprehensive understanding of chordoma biology is needed. To that end, scientists at the University of Toronto are applying cutting-edge analyses to systematically survey multiple aspects of chordoma biology and integrate the resulting data to paint a fuller and more nuanced picture of this disease.
This project is part of the Chordoma Foundation’s coordinated multi-omics strategy involving investments in multiple complementary projects that, together, will create the most complete picture of chordoma possible with today’s technology.
The first phase of this work was funded by the Chordoma Foundation and the Canadian Cancer Society (CCS) in 2018. With that grant, Dr. Gelareh Zadeh, together with graduate student Jeffrey Zuccato and colleagues, used state-of-the-art techniques to systematically survey chordoma’s epigenetic landscape — changes to DNA that affect which genes are turned on and off — using a large cohort of chordoma tumor samples from three international neurosurgical centers.
Encouragingly, Dr. Zadeh’s team discovered two clearly defined molecular subtypes of chordoma based on epigenetic changes in the tumor cells. Importantly, the investigators also found that these subtypes are predictive of prognosis, and that patients with different subtypes may benefit from different treatment approaches. The findings represent a significant step toward informing personalized treatment approaches for chordoma patients.
We’re grateful for our partnership with CCS, which was made possible through the dedicated fundraising efforts of the Canadian members of our Board of Directors, Steven Golick and Ed Les.
Based on initial findings, the researchers are applying existing drugs known to regulate epigenetic changes to chordoma cell lines, and have identified a subset of drugs that have apparently shown early promise in reducing growth of the cell lines.
More recently, Dr. Zadeh has forged a partnership with Dr. Thomas Kislinger, also at U of T, who is one of the world’s leading experts in cancer proteomics. Their goal is to discover proteins on the surface of chordoma cells that could serve as targets for a variety of emerging treatment modalities — like systemic therapies that selectively target tumor cells, and various types of immunotherapy. These approaches are proving to be highly effective against many other cancers, and this project could soon open the door to applying them to chordoma as well.