For more than three decades, internationally renowned neurosurgeon Dr. Chandra Sen, the Bergman Family Professor of Skull Base Surgery at NYU Langone Health, has provided expert surgical care to patients with chordoma and other skull base tumors. Now, Dr. Sen – a...
Target Discovery Initiative
Systematically uncovering chordoma’s most promising vulnerabilities
The new paradigm of precision oncology relies on the identification of specific molecular features in cancer cells that are essential to their growth and survival, called “therapeutic targets.” Hence, finding effective treatments for chordoma depends first and foremost on illuminating such vulnerabilities. These targets could be, for example, certain proteins upon which tumor cells are uniquely dependent for survival, processes that are inappropriately activated in tumor cells, or calling cards of tumor cells to which therapies can be directed.
Our Target Discovery Initiative aims to systematically uncover the most promising therapeutic targets in chordoma among the vast number of possible therapeutic targets that exist within tumor cells. The Initiative is guiding the redirection of existing treatments to chordoma (drug repurposing) or, if necessary, the development of new drugs against currently inaccessible targets.
Strategy
The Chordoma Foundation is supporting a broad portfolio of projects employing cutting-edge technologies to uncover aspects of chordoma biology that could serve as therapeutic targets. Key areas of focus include:
- Mapping the spectrum of chordoma dependencies: creating a deep understanding of the genes and proteins upon which chordoma cells depend for growth or survival
- Conducting multi-omic analyses: characterizing alterations in genes (genome), gene expression (epigenome), proteins (proteome), and additional “omes” to paint a comprehensive, multi-layered picture of chordoma biology
- Understanding the chordoma microenvironment: learning how chordoma interacts with immune cells and surrounding tissues
Impact
As potential targets are identified, we partner with researchers to determine the fastest path to new treatment options for chordoma patients. Our Target Dashboard summarizes data collected on altered genes, proteins, and cellular circuitry that may directly serve as, or indirectly point to, therapeutic targets in chordoma.
To date, this research has pointed to more than 30 potential targets, most of which already have corresponding therapies either approved in other cancer types or in development. We are actively exploring many of those through our Drug Repurposing Initiative.
Most notably, however, this research revealed the protein brachyury, a hallmark of chordoma, to be the key driver and greatest vulnerability of chordoma cell lines and has thus motivated an aggressive push to create the first brachyury drugs through our Brachyury Drug Discovery Initiative.
Projects
| Mapping the spectrum of chordoma dependencies | Stuart Schreiber, PhD, and Tanaz Sharifnia, PhD – Broad Institute | Ongoing |
| University of Toronto multi-omics projects | Gelareh Zadeh, MD, PhD, and Thomas Kislinger, PhD – University of Toronto | Ongoing |
| 101 chordoma multi-omes | Stefan Fröhling, MD – German Cancer Research Center and National Center for Tumor Diseases | Ongoing |
| Multidimensional epigenome-metabolome integration for human chordoma subclassification | Andrew Venteicher, MD, PhD – University of Minnesota | Ongoing |
| Understanding molecular and cellular bases of tumor hypoxia and immune evasion in chordomas | Chandranath Sen, MD – NYU Langone Health | Ongoing |
| Multispectral immunofluorescence of chordoma | Nyall London, MD, PhD – Johns Hopkins | Ongoing |
| Generation of a targeted drug discovery platform and next generation sequencing in chordoma | Cameron Brennan, MD – Memorial Sloan-Kettering Cancer Center | Complete |
| Multi-omic study of the epigenetic landscape of chordoma | Adrienne Flanagan, MD, PhD – University College London Cancer Institute | Complete |
| Making chordoma more susceptible to immune attack | Stephen Yip, MD, PhD – University of British Columbia | Complete |
News
New grant will support chordoma immunotherapy research at Johns Hopkins Medicine
Immunotherapy is an approach that harnesses patients’ own immune systems to recognize and destroy their tumors. In recent years, it’s shown tremendous promise against several cancers. To ensure that chordoma patients benefit from these advances as well, investing in...
New research investment to reveal chordoma subtypes, drivers of metastasis
The Chordoma Foundation is thrilled to have awarded two new $250,000 research grants aimed at generating a more complete picture of chordoma biology. The funds will support teams led by investigators at the University of Minnesota (U of M) and the German Cancer...
Grants awarded to two Canadian researchers address key research priorities in chordoma
At the end of 2018, the Chordoma Foundation and the Canadian Cancer Society (CCS) together awarded two new grants totaling $300,000 to Canadian researchers whose work in epigenetics and immunotherapy stand to have a lasting impact on chordoma treatment and care. The...
Veteran cycler and chordoma survivor advance cutting-edge chordoma research at Dana-Farber Cancer Institute
In their nearly 30 years of friendship, Todd Balf and Chris McKeown have cycled thousands of miles together. From treks across New England to a week-long ride through the Rocky Mountains, they’ve shared a passion for biking and a thirst for adventure that withstood...
Progress in chordoma research serves as a template for other rare cancers
Since the Chordoma Foundation started, we have been driven by the belief that success in enabling and accelerating research for chordoma would not only lead to the cure we seek, but also inform new approaches for other rare cancers. We are, therefore, delighted that a...
Results of the Chordoma Genome Project reveal genetic changes that drive chordoma
Why mutations matter All cancers are the result of abnormal changes (“mutations”) in DNA which cause uncontrolled growth of the cells in which the changes occur. Modern cancer drugs target and kill cells that harbor specific cancer-causing mutations while sparing...
Embarking on a systematic search for better ways to treat chordoma
I’m excited to announce that we have embarked on a multi-year partnership with the Center for the Science of Therapeutics at the Broad Institute of Harvard and MIT to systematically uncover new therapeutic targets for chordoma—aspects of chordoma’s biology that could...