Potential Treatment of Chordoma With PI3K Inhibitors

Key Points

  • 16% of the chordoma tumor samples had genetic changes mutations in PI3K signaling genes.
  • The brachyury gene (T), has been known for some time to play a role in chordoma, but the research team demonstrated that only one additional copy of the T gene seems to drive these tumors.
  • The team also discovered a new cancer gene that is specific to chordoma, known as LYST, which has not been found in any other cancer.

Patients with chordoma—a rare bone cancer of the skull and spine—could be helped by existing treatments, suggest scientists from the Wellcome Trust Sanger Institute, University College London Cancer Institute, and the Royal National Orthopaedic Hospital NHS Trust. In the largest genomics study of chordoma to date, published by Tarpey et al in Nature Communications, scientists show that a group of chordoma patients have mutations in genes that are the target of existing drugs, known as PI3K inhibitors.

Researchers suggest a clinical trial of PI3K inhibitors for this particular group of chordoma patients, who could benefit from existing treatments.

Chordoma is a rare form of bone cancer that strikes individuals of all ages. Chordomas are slow-growing yet aggressive tumors that form in the vertebral bodies of the spine, the sacrum, and base of the skull. The cancerous tumor is considered to develop from persistent embryonic tissue, known as the notochord. As they involve critical structures such as the brainstem, spinal cord, and important nerves and arteries, chordomas are difficult to treat. Surgery and radiation are currently the only effective forms of treatment.

Study Findings

For the first time, scientists have used whole-genome sequencing to gain a better understanding of the biology underlying chordoma. The results reveal promising new treatment options for a cancer with a poor prognosis.

The team studied chordoma tumors from 104 patients and found that 16% of the tumor samples had genetic changes mutations in PI3K signaling genes. These genes are the target of existing drugs, known as PI3K inhibitors, which are being used to treat many cancers, including breast cancer, lung cancer, and lymphoma, but have not yet been considered for chordoma.

The brachyury gene (T), has been known for some time to play a role in chordoma, but for the first time the team used genomic sequencing to demonstrate that only one additional copy of the T gene seems to drive these tumors. The team also discovered a new cancer gene that is specific to chordoma, known as LYST, which has not been found in any other cancer. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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