A new study conducted by the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of Medicine has demonstrated that a carboplatin and everolimus combination could help treat paediatric glioma, a type of brain tumour.
Carboplatin is a routinely prescribed chemotherapy drug, while everolimus blocks the mTOR enzyme that is linked to tumour growth.
The combination, which is intended for resistant and recurrent low-grade gliomas, was found to induce DNA damage and cell death during preclinical testing.
Specifically, the combination slowed tumour growth and killed tumour cells in laboratory and mouse models.
Paediatric low-grade glioma is the most common brain tumour and said to recur in approximately 50% of patients treated for low-grade glioma. Moreover, recurring tumours are often resistant to chemotherapy.
When carboplatin was used as a monotherapy, four different human cell lines of low grade glioma did not show any response or kept growing. Similarly, certain cell lines were resistant to everolimus alone.
The researchers then combined the drugs and treated the same cell lines, which died or grew slower. The results were repeated in mouse models without any added toxicity.
Johns Hopkins Kimmel Cancer Center oncology associate professor Eric Raabe said: “We saw dramatic growth inhibition after only a low concentration of everolimus was combined with the carboplatin.
“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 2014, a clinical study by the researchers validated the safety of everolimus in paediatric low-grade glioma. While some patients responded to the medicine, the team did not analyse tumours tissue from those patients to gain better insights into the molecular role of mTOR.
Currently, a study in paediatric low-grade glioma is being conducted to assess tumour tissue from each patient for expression of mTOR markers that could help predict response to everolimus.
Raabe noted: “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.”