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First International Chordoma Research Workshop: summary and outcomes

by

Simone Sommer, MD, MPH

Co-Founder

Chordoma Foundation

 

Josh Sommer

Co-Founder

Chordoma Foundation

 

Chordomas are primary bone malignancies and a type of sarcoma. Chordomas are thought to arise from ectopic rests of notochordal remnant cells with an estimated prevalence of .8 per million. The anatomical distribution of these tumors mirrors the occurrence of notochord remnants, (29% in the sacrum and 32% in the clivus) [1]. Treatment of chordomas is predominantly surgical followed in most cases by postoperative adjuvant radiotherapy with photons or protons [2]. Due to frequent recurrence, five and ten-year survival rates for chordoma patients are 68% and 40%, respectively [1]. Historically, research on chordoma has been conducted in isolation and in a fragmented manner since it has not been included in any existing disease advocacy group. Thus, in February of this year, the Chordoma Foundation was incorporated as a new nonprofit organization that is initiating a coordinated, international, multidisciplinary initiative to develop targeted diagnostic and improved therapies for chordoma. The Chordoma Foundation serves as a bridge between patients, doctors, researchers and governmental agencies, representing the interests of those with chordoma, and instilling a sense of urgency in the process of developing improved treatments.

 

On May 3-4, 2007 the First International Chordoma Research Workshop (1st ICRW) was co-hosted by the Chordoma Foundation, the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), the National Institute for Neurological Disorders and Stroke (NINDS) and the NIH Office of Rare Diseases (ORD). This workshop was conceived to initiate a coordinated, logical and deliberate research effort among collaborators from various biomedical disciplines, and to bring new basic-science researchers into the emerging chordoma research community. The multi-disciplinary group included neurosurgeons, orthopedic surgeons, radiation and medical oncologists, neurologists, neuroradiologists, geneticists, embryologists, biomedical engineers and cell biologists. In addition, executives of the Genetic Alliance and the Tuberous Sclerosis Alliance provided perspectives from other successful advocacy/research organizations. Fifty-three participants attended from Japan, UK, Italy, Canada, and top academic centers in the US, such as Harvard, Memorial Sloan Kettering, Johns-Hopkins, MD Anderson, Duke, and the University of Pittsburgh. The excitement in the room was palpable as former strangers united as a team in pursuit of a common goal. The level of collegiality among attendees was unprecedented. Dr. Francis Collins, director of NHGRI, moderated the workshop and facilitated the development of a roadmap for the future of chordoma research. This landmark event was an exciting opportunity to chart the course towards finding better treatment options and ultimately curing chordoma.

 

The workshop's agenda included both plenary and small working group sessions that focused on three key topics: 1) clinical management; 2) mechanisms of disease; and 3) therapeutic development. Each working group set goals for advancing the field and then identified resources and specific actions needed to accomplish those goals. [4] Breakout group moderators compiled this information and presented it to the larger group for discussion. What emerged was broad consensus on a comprehensive plan for conducting basic science, translational, and clinical research in parallel.

 

The Chordoma Foundation serves as a hub for organizing and directing research, and currently has initiated and facilitated twelve interdisciplinary research projects.

 

Chordoma Foundation Research Collaborations

  1. Microarray based gene expression analysis, and candidate gene knockdown – Michael Kelley, MD; Duke University (September 2006)

  2. Genome-wide tumor profiling – Paul Meltzer, MD, PhD; National Cancer Institute (January 2007)

  3. Examining the therapeutic value of the High Molecular Weight Melanoma Associated Antigen (HMW-MAA) in chordoma and exploring the ferret as an animal model– Soldano Ferrone, MD, PhD; University of Pittsburgh and Christina Antonescu, MD; Memorial Sloan Kettering (January 2007)

  4. High Throughput Small Molecule Screening – Michael Kelley, MD; Duke University and Chris Austin, MD; National Chemical Genomics Center (February 2007)

  5. Examining the role of the TSC/mTOR pathway in chordoma – Vijaya Ramesh, PhD and Andrew Rosenberg, MD; Mass General Hospital (February 2007)

  6. Exploring tractable cell-signaling pathways in chordoma – Neil Spector, MD; Duke University (February 2007)

  7. Exploring the hedgehog pathway in chordoma – Wei Chen, PhD; Duke University (March 2007)

  8. In-vitro screening of novel preclinical compounds – Andrew Wagner, MD, PhD; Dana Farber Cancer Institute (June 2007)

  9. Developing targeted liposomal nanoparticles for imaging chordoma – Srinivasan Mukundan, MD, PhD; Duke University (April 2007)

  10. Familial Chordoma Study – Dilys Parry, PhD; National Cancer Institute and Michael Kelley, MD; Duke University (May 2007)

  11. Brachyury targeted T-cell immune-therapy for chordoma – Jeffrey Schlom, PhD; National Cancer Institute (June 2007)

  12. The study of notochord in relation to chordoma pathogenesis – Andrew Rosenberg, MD; Mass General Hospital (June 2007)

Research projects are often hampered by non-scientific factors including: access to tissue and cell lines, information sharing, communication, partnership and licensing issues, and funding. Only an independent outcome-driven organization can take the birds-eye-view approach needed to overcome these obstacles and accelerate the pace of research on a rare condition like chordoma. As such, a primary near-term aim is to establish a clinical data and biospecimen repository that will, for the first time, provide chordoma tissue and cell lines to the scientific community, and will allow researchers to match biological data with clinical outcomes.

 

In an attempt to rapidly enact the roadmap developed at the 1st ICRW, and encourage rapid drug discovery, the Chordoma Foundation has laid out a multi year strategic plan that will catalyze the development of targeted diagnostics and therapies. This plan can be divided into three primary phases (Phase 1-3).

 

 

With a roadmap to guide research efforts now in place, and a dedicated team of researchers ready to act, the Chordoma Foundation is now preparing to begin Phase 1 of its Research Plan

 

Phase 1 will last approximately two years and cost $2 million. The primary goal during Phase 1 is to foster discoveries that will lead to the rational development of targeted therapies. During this phase the Chordoma Foundation will:

 

  1. Set up an efficient and capable research support infrastructure

Tissue and cell line BioBank, clinical data repository, online knowledgebase, communications networks

  1. Develop research tools

Cell lines, tissue microarrays, animal models, cell-based assays

  1. Provide seed funding to researchers

Molecular pathology, cellular and developmental pathways, genetics & genomics, drug screening

  1. Conduct genome-wide tumor profiling projects

Gene expression microarray, array CGH, genotyping, sequencing

  1. Create expert recommendations

Clinical Management Guidelines Committee, Clinical Trials Working Group, professional societies

 

Progress will be assessed at yearly research workshops and the roadmap will be adjusted as new data becomes available. The Second International Chordoma Research Workshop is scheduled for April 2008. Click here to request more information.

 

[Editor's Note: Josh, who is pursuing an undergraduate degree in biomedical engineering at Duke University, has been conducting chordoma-related research in Dr. Mike Kelly’s lab and is collaborating with Duke researchers Neil Spector, Srini Mukundan, and Wei Chen. It’s particularly inspiring to know that Josh is also a recent chordoma survivor.]

 

[Editor's Note: The Liddy Shriver Sarcoma Initiative recently funded a chordoma research project being undertaken by Dr. Silvana Pilotti in the Laboratory of Experimental Molecular Pathology of the Department of Pathology at the Fondazione IRCCS Istituto dei Tumori in Milan, Italy. You can read more about this study by clicking here. Given the research agenda discussed in this article, we hope that opportunities will arise in the future to cofund chrodoma research with the Chordoma Foundation.]

 

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References

[1] McMaster, M. L., et al., 2001. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control. 12, 1-11.

[2] Hug, E. B., 2001. Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus. 10, E11.

 

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