New marker for bone cancer prognosis could lead to life-saving treatments

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Researchers have found a way to identify which patients with a rare bone cancer are least likely to be cured by the current standard treatment.

In a study funded by the Bone Cancer Research Trust and the Ewing’s Sarcoma Research Trust, researchers from the University of Leeds were able to pinpoint the particular cancer cells – known as cancer stem-like cells – in Ewing sarcoma that are resistant to chemotherapy and responsible for recurrence of the disease.

The study has been published in Cellular Oncology.

Lead researcher Professor Sue Burchill, from the University of Leeds’ School of Medicine, said: “The initial clinical impact from this research is the ability to identify those patients with localised disease who experience the poor outcomes normally associated with patients who have disease in multiple parts of the body. If doctors can use high levels of neurexin-1 to identify these patients at an early stage and treat them with a stronger combination of drugs, this could increase survival for some patients.”

Ewing sarcoma

Ewing sarcoma is a rare type of cancer that affects bones or the tissue around bones. It is seen mainly in children and young people, but can also be diagnosed in adults. For around one in three patients diagnosed with Ewing sarcoma in just one part of the body, current treatments are ineffective. The research team hopes that the new findings will help to make more treatments available to these patients and increase their chance of survival.

Currently, chemotherapy, radiotherapy, and surgery increase long-term survival in between 55% and 65% of patients who are diagnosed with localised cancer. However, the other patients see their disease progress and suffer a relapse. For these patients, the outcomes are as poor as those diagnosed when the cancer has already spread.

Working with surgeons from the Royal Orthopaedic Hospital in Birmingham and the Translational and Clinical Research Institute at the University of Newcastle, the team was able to use samples of tumour tissue from Ewing sarcoma patients and grow the cells in the laboratory.

Neurexin-1 protein

In the laboratory, the research team discovered a protein called neurexin-1 at much higher levels in the cancer stem-like cells. They then looked at survival data and found that patients whose tumours had higher levels of this protein were more likely to see the disease return and less likely to survive.

Dr Elizabeth Roundhill, Research Fellow at the University of Leeds, explained: “Tumours are a mix of different cells which interact with each other and with cells of the surrounding environment to grow and spread. However, cancer stem-like cells are different: they can divide and multiply independently of other cells in the tumour and can initiate new tumour spread and growth. These are the particularly dangerous cells we wanted to find.”

From each sample, the team took approximately 1000 single cells to identify those that were able to grow and were resistant to current chemotherapy. Using state-of-the-art RNA sequencing, the researchers were able to see that neurexin-1 was expressed at high levels in these cancer stem-like cells.

The team is already working with colleagues in Spain, Italy and Switzerland on a large study comparing neurexin-1 with other possible markers, to validate the best way to identify patients who need treatment that is more intensive. They hope to have the results of this study later this year. If the study confirms their findings, the next stage would be to use neurexin-1 to select patients for treatment in a clinical trial.

Potential for new treatment

Dr Zoe Davison, Head of Research, Information and Support at the Bone Cancer Research Trust, said: “This research marks an incredibly significant find in understanding and predicting which patients may not respond to the standard chemotherapy treatment for Ewing sarcoma. By understanding this, it may lead to new and more effective ways to treat these patients. We are delighted that we have been able to fund this vital work on multiple occasions, which demonstrates the importance of consistent funding to enable research to progress and succeed.”

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