Targeting the Ras/MAPK pathway for treatment of high-grade pediatric brain tumors

Brain cancer is an extremely aggressive disease that remains difficult to cure and carries a high mortality rate. Every year, more than 3,500 children in North America are diagnosed with this disease. Brain tumours are the most common solid tumours and the second leading cause (after leukemia), of cancer-related deaths in children. The majority of patients (80 percent), with the more aggressive forms of brain tumours will survive less than two years. Surgical removal of brain tumours is challenging for a number of reasons, and complete removal of cancer cells is virtually impossible. The chemotherapeutic agent Temozolomide (TMZ), is used in patients with aggressive brain cancers however, in a subgroup of patients this drug does not work effectively because they are resistant to it. Furthermore, recent research shows that TMZ is not generally very effective at eliminating pediatric brain tumour cells. Consequently, certain 'survivor' tumour cells become 'seeds', generating more cells that subsequently form a new tumour. Cathy Lee's research focuses on a protein called PLK1, which is essential to the cell division process in cancer cells. Many researchers have shown that PLK1 levels are higher in cancer cells than in normal cells and that tumour cells require this protein for survival. When this protein is eliminated, cancer cells either die or their growth is suppressed. Importantly, normal cells do not seem to be greatly affected by PLK1. Ms. Lee's research will provide a deeper understanding of this protein. In related research, Lee will examine the 'seeds' of brain tumours, called 'brain tumour initiating cells', with a view to determining a way to prevent their expansion and induce cell death. The results of her research will improve our understanding of pediatric brain cancers and allow future design of novel, alternative therapeutic strategies that benefit patients' health and improve the way we currently treat this devastating disease.