Brain tumours are the leading cause of cancer-related death in children and are among the most challenging childhood cancers to treat. Medulloblastoma is the most common malignant brain cancer of childhood. Surgery followed by radiotherapy and chemotherapy are the mainstays of front-line treatment. The overall survival rates for medulloblastoma patients have not improved for decades, and the impact of the current treatment is devastating, producing long-term sequelae in survivors. Thus, there is an urgent need to identify more effective therapeutic strategies for medulloblastoma that have potential to improve survival rates and reduce treatment-related toxicity. A large body of evidence has demonstrated that cannabinoids, the active compounds of the plant Cannabis sativa, exert anti-tumour actions in different cancer types. Moreover, it has been shown that cannabinoids can improve the effect of chemotherapy and radiotherapy in glioblastoma models. Although there is growing evidence about the anti-tumour properties of cannabinoids in adult cancers, there is very little data about their effect on paediatric tumours. In particular, there is no existing data in paediatric brain tumour models. In this context, we aimed to determine if cannabinoids, both pure compounds and whole plant extracts (WPE), have anti-tumour efficacy in medulloblastoma either alone and in combination with conventional chemotherapies.
Here we show that different paediatric brain tumour types express both cannabinoid receptors, CB1 and CB2. We further investigated the effects of cannabinoids in three patient-derived group3 medulloblastoma cell lines and show that pure-THC, pure-CBD, WPE-THC and WPE-CBD reduce the viability of these cells. This effect is mediated, at least in part, by CB2 and by the production of reactive oxygen species. Furthermore, cannabinoids induce apoptosis in medulloblastoma cells and target the mTORC1 signalling pathway. Additionally, cannabinoids interact in an additive manner with conventional chemotherapeutics cyclophosphamide and gemcitabine.
These results suggest that cannabinoids could be an interesting therapeutic tool for the management of medulloblastoma. Current work is investigating the therapeutic potential of these agents using preclinical models.