Funding outcome

Gliobastoma is a devastating cancer in children with a 5-year survival rate of less than 20%. Over 1/2 of these tumors occur in the midline of the brain, where the vital control centres of heart rate and breathing are. The tumors are known to be highly proliferative, very invasive and extremely resistant to current therapies. Because of this, midline brain gliomas or diffuse interstitial pontine gliomas (DIPGs) have a 5-year survival rate of under 2%. Glioblastomas have not seen an improvement in therapy in the last 20 years, and is currently restricted to limited surgical excision, radiotherapy and chemotherapy. Though recent studies have dramatically improved our knowledge of the biology and molecular anatomy of these tumors, translation to new therapies has continued to lag behind. Moreover, most approaches to cancer are currently highly invasive, and toxic to normal cells, particularly in the young developing brain. It is clear that new and perhaps daring approaches are desperately needed. Recent work in the field of cancer has begun to focus on the development of safer initiatives, and has turned to nutritiional approaches. This line of thinking has followed the epidemiologic and anecdotal findings that cancer is generally reduced in those populations where fruits and vegetables are eaten frequently. Sulforaphane, a metabolite produced from the combination of glucosinolates and myrosinase in cruciferous vegetables, has been investigated for the treatment of a variety of cancers since the early 1990's. It has been found to be safe metabolite which has a profoundly beneficial effect on the proliferation, invasiveness and anti-therapeutic effects. Several studies have shown this benefit in glioblastoma cell lines as well. The ketogenic diet (KD) is known to have a beneficial effect on epilepsy control in children since the 1920's, and continues to be utilized for this disorder. Recently however, the KD has been shown to have beneficial effects on a variety of neurologic disorders, including the treatment of glioblastoma. The idea behind this is related to the fact that cancers are known to require high concentrations of glucose for their survival and aggressiveness. The KD switches the metabolism of the tumor to ketone bodies, which is not ideal for tunors, and hence they are not able to survive. Our laboratory has been involved in the study of both sulforaphane and the ketogenic diet as beneficial approaches to treating perinatal brain damage. We are now turning to investigating these therapies in combination to benefit outcome from glioblastoma and provide safe and innovative treatments, with the potential to improve the life of children and their families with this uniformly deadly cancer.