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Patients with chordoma, the rare, recurring bone cancer of the skull and spine, are surviving longer, according to data reported at the Third International Chordoma Research Workshop, held in Bethesda, Maryland.


In a reanalysis of nationwide cancer registry Mary McMaster, MD, from the National Cancer Institute's Genetics Epidemiology Branch found that the median survival of chordoma patients has increased from seven to nine years.


As explained in a news release from the Chordoma Foundation, among the other findings reported at the meeting, attended by 85 physicians and scientists from 31 institutions from nine different countries, as well as for the first time, four pharmaceutical companies, are that genomic analysis has revealed mutations that could be driving chordoma, that the gene brachyury is a promising target, that new cell lines are in development, that new mouse models of chordoma have been developed, and that two clinical trials are nearly finished and that three additional ones are set to open soon.


Researchers from the Sanger Institute, the NIH Intramural Sequencing Center, the British Columbia Cancer Agency, and Massachusetts General Hospital presented preliminary findings from analyzing the chordoma genome with a variety of technologies including exome sequen-cing, paired-end rearrangement analysis, kinome sequencing, and transcriptome sequencing.


Mutations were identified in several known cancer genes including PTEN, Akt, and PI3K, which belong to a signaling pathway recently discovered to be highly active in chordomas. Work is ongoing to increase the number of samples sequenced and determine the functional significance of the mutations identified.


Several speakers presented data suggesting that the brachyury plays an important role in driving chordoma as well as other types of cancer. Adrienne Flanagan, MD, PhD, of University College London and Wesley Hsu, MD, of Johns Hopkins University both found that knocking down the brachyury causes chordoma cells to stop growing, apparently indefinitely.


Work is ongoing at both institutions to develop ways to knock down brachyury in chordoma tumors. Additionally, NCI researchers are working on an immune therapy approach to selectively destroy cells that express brachyury.


Researchers from Massachusetts General Hospital, Johns Hopkins University, Medical University of Graz in Austria, and the University of Ulm in Germany all reported on new chordoma cell lines at various stages of development. Each of these groups continue to work on developing new cell lines, and have promised to contribute their cell lines to the Chordoma Foundation cell line panel once they are fully validated. The Foundation noted that so far it has distributed the two cell lines in its cell line panel to 33 different labs.


Researchers from Massachusetts General Hospital, Johns Hopkins University, and Istituto dei Tumori in Milan presented detailed characterization of five newly developed mouse xenograft models of chordoma (human chordoma tumors grown inside mice). These researchers and others have been trying unsuccessfully for years to get chordomas to grow in mice (until now only one xenograft had been reported), but have now learned methods that increase the odds of success.


Clinical Trials

Regarding the clinical trials, the Sarcoma Alliance for Research through Collaboration (SARC) has enrolled 34 chordoma patients on the Phase II SARC009 study of dasatinib. Scott Schuetze, MD, PhD, of the University of Michigan presented preliminary data showing that dasatinib induced disease stabilization in a number of patients-some for longer than two years.


Silvia Stacchiotti, MD, of Istituto dei Tumor reported final results from a Phase II study of imatinib in 50 chordoma patients. Over sixty percent of patients treated with imatinib experienced a partial response or stable disease for at least six months, she said, and her group has also opened two new Phase II trials with targeted therapies for patients with advanced chordoma: one with imatinib plus the mTOR inhibitor RAD001, and one with the EGFR/HER2 inhibitor lapatinib.


In addition, Deric M. Park, MD, from the University of Virginia has opened a Phase Ib trial of imatinib in combination with the HDAC inhibitor LBH589, enrolling patients from his institution as well as the University of Michigan and Massachusetts General Hospital.


Chordoma Foundation

The nonprofit Chordoma Foundation ( was started in 2007 by Simone Sommer, MD, MPH, and her son Josh, after he was diagnosed with a chordoma in 2006, during his freshman year at Duke University. Soon after his diagnosis, Josh Sommer, now Executive Director of the Foundation, joined the lab of the only federally funded chordoma researcher, Duke oncologist Michael Kelley, MD, learning about cell line characterization, gene-expression microarray analysis, candidate gene knockdown using RNA interference, and in vitro drug screening. After finishing his junior year in 2008, Sommers was awarded a two-year fellowship for social entrepreneurs, and subsequently took a leave of absence from Duke. He is now back as part of Duke's Program on Global Health and Technology Access as a Fellow in Strategic Philanthropy and Health, and continues to participate in research in the Kelley lab, and helps coordinate collaborations with a network of chordoma researchers at other institutions around the world.