A new combination of drugs involving carboplatin and everolimus may help slow tumour growth in paediatric brain cancer, according to a study published in Neuro-oncology.
Researchers at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of medicine have used the mTOR enzyme inhibitor everolimus along with carboplatin to treat resistant and recurrent low-grade glioma in laboratory mice models. The enzyme mTOR was earlier found to help in the growth of these tumours. The findings from the study revealed an increase in DNA damage and cell death in tumours among the mice models.
Paediatric low-grade glioma is a common form of brain tumour in children. They can often be treated with surgery alone. However, when these tumours occur in locations such as near optic nerves or in the mid-brain area, surgery often becomes too risky. The tumours may also have a tendency to grow back after surgery.
“Tumours recur in about 50 percent of patients treated for low-grade glioma and require additional treatment with chemotherapy. Recurring tumours are often resistant to chemotherapy.” said Eric Raabe, M.D., Ph.D., associate professor of oncology and paediatric brain tumour expert at the Johns Hopkins Kimmel Cancer Center, in a press release.
Researchers revealed that on treating with carboplatin alone four different human cell lines of low-grade glioma showed to have no response or kept growing, while some cell lines were resistant to everolimus alone. Treating the cell lines with a combination of carboplatin and everolimus showed more prominent cell death or slower growth. The study confirmed 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,” said 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.”
A previous clinical study conducted by Raabe and other researchers in 2014 had already helped confirm safety of the mTOR-blocking drug everolimus in patients with paediatric low-grade glioma in which some patients showed to respond to the drug.
“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,” said Raabe. “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.”