Chordoma Foundation

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

 Project

Principal Investigator(s)

Status

Mapping the spectrum of chordoma dependencies Stuart Schreiber, PhD, and Tanaz Sharifnia, PhD – Broad Institute Ongoing
Analysis of the epigenetic landscape of chordoma Gelareh Zadeh, MD, 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

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...

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