Largest genomics study of chordoma reveals potential new treatment option

The largest genomics study to date of chordoma, a rare bone cancer of the spine and skull, has discovered a group of patients who possess mutations in genes known to be targets of existing drug-PI3K inhibitors.

This study performed by a team from the Wellcome Trust Sanger Institute, University College London Cancer Institute and the Royal National Orthopaedic Hospital NHS Trust (all London, UK) was recently published in Nature Communications.  The team suggests a further clinical trial investigating P13K inhibitors could be beneficial for chordoma patients who possess these mutations.

Due to their slow-growing but aggressive nature, chordomas have a poor prognosis.  The only effective treatment options currently are surgery and radiation therapy.  These options have a high risk associated with them due to the tumors placement and potential involvement of surrounding critical structures, such as the brainstem, spinal cord or important arteries. This study was the first to utilize whole genome sequencing in order to gain a better understanding of the biology underlying chordoma.

Chordoma tumors from 104 patients were investigated and 16% of the tumor samples possessed genetic mutations in PI3K signalling genes. These genes are the target of existing drugs, known as PI3K inhibitors, which are being used to treat many other cancers, including breast cancer, lung cancer and lymphoma, but have not previously been considered for chordoma [1].

We recently spoke with the lead author of this chordoma study, Peter Campbell from the Wellcome Trust Sanger Institute (Cambridge, UK) about his work in identifying the preventable causes of cancer. >>> Watch the full video interview here.

Joint first author Sam Behjati, from the Wellcome Trust Sanger Institute, explained: “By sequencing the tumors’ DNA, we get a much clearer view of the genetic changes that drive chordoma. We have shown that a particular group of chordoma patients could be treated with PI3K inhibitors, based on their mutations. This would have been missed had we not done genomic sequencing of their tumors.”

It is well established the gene brachyury, or T, has a role in chordoma development. However, the research team was also able to demonstrate, with genomic sequencing; only one additional copy of the T gene appears to be involved in chordomas. Additionally, they believe to have discovered a new cancer gene specific to chordoma, known as LYST.

Adrienne Flanagan, joint lead author from the Royal National Orthopaedic Hospital NHS Trust and University College London Cancer concluded: “This study provides a resource for chordoma research for years to come. In the future we hope to target chordoma from three angles: trialing PI3K inhibitors in chordoma; developing a therapeutic approach to switching off the extra copy of the T gene and studying the function of LYST as a cancer gene and its role in the development of chordoma”.


Tarpey B, Behjati S, Young MD et al. The driver landscape of sporadic chordoma. Nat. Comm. doi: 10.1038/s41467-017-01026-0 (2017); Eureka alert press release

[1] Massacesi C, Di Tomaso E, Urban P et al. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design Onco. Targets Ther. doi: 10.2147/OTT.S89967 (2017)