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New combination treatment for kids can help treat paediatric brain tumour: Study

New combination treatment for kids can help treat paediatric brain tumour: Study
Paediatric low-grade glioma is one of the most common brain tumour among children. ©Shutterstock

A new study by Neuro-Oncology Journal identifies a novel combined treatment involving carboplatin, a standard chemotherapy drug that works well against these brain tumours, and everolimus, which blocks an enzyme called mTOR that accelerates the growth of brain tumour in kids.

Written by ANI |Published : March 22, 2019 6:09 PM IST

According to a new study published in the Neuro-Oncology Journal, researchers have identified a new combination treatment for kids suffering from brain tumour. The novel treatment is targeted at resistant and recurrent low-grade gliomas slowed tumour growth and killed tumour cells in laboratory and mouse models.

Notbaly, paediatric low-grade glioma is one of the most common brain tumour among children and it can be cured with the help of surgery. However, in some people, the location of the tumour can make the task of surgeons difficult, as tumours near optic nerves or in the mid-brain area, or tumours that recur post-surgery can be difficult to treat.

Researchers at the Johns Hopkins Kimmel Cancer Centre and the Johns Hopkins University School of Medicine combined carboplatin, a standard chemotherapy drug that works well against these brain tumours, and everolimus, which blocks an enzyme called mTOR that was shown in earlier research to fuel the growth of these tumours. The combination increased DNA damage and cell death in laboratory models. Eric Raabe, M.D., Ph.D., associate professor of oncology and paediatric brain tumour expert at the Johns Hopkins Kimmel Cancer Centre, says tumours recur in about 50 per cent of patients treated for low-grade glioma and require additional treatment with chemotherapy. Recurring tumours are often resistant to chemotherapy.

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The researchers wondered whether combining carboplatin and everolimus would be more effective. When treated with carboplatin alone, four different human cell lines of low grade glioma cancer cells did not respond to the drug or kept growing. Similarly, some cell lines were resistant to everolimus alone. When they treated the same cell lines with a combination of carboplatin and everolimus, the cells died or grew slower, and the researchers saw similar results in mouse models with no added toxicity."We saw dramatic growth inhibition after only a low concentration of everolimus was combined with the carboplatin," informed Raabe. "We found that everolimus disrupted a key mechanism the cancer cells use to detoxify carboplatin. The ability of everolimus to increase the power of carboplatin suggests this combination could be used effectively in patients."

In a previous clinical study in 2014, Raabe and other researchers were able to confirm the safety of the mTOR-blocking drug everolimus in patients with paediatric low-grade glioma and found some patients responded to the medicine. However, they never tested tumour tissue from those patients to understand the molecular role of mTOR. "The current nationwide clinical study of everolimus in paediatric low-grade glioma requires that some tumour tissue from each patient be evaluated for expression of mTOR markers that might predict response to everolimus," Raabe said."In this way, we hope to figure out who is most likely to respond to the drug, so that we can move closer to our goal of giving the right medicine to the right patient at the right time.

In the future, we may be able to give everolimus along with carboplatin to patients with high-level mTOR expression. Based on our research, we predict that these tumours will likely be resistant to carboplatin unless we simultaneously block mTOR."