Grant: CIHR Fellowship

While the 5-year survival rates for children with cancer continue to improve, the major problem of drug-related side effects remains. For example, the cancer therapy drug, methotrexate, can save a child's life, but it can also lead to mucositis, a painful inflammation of mucosal linings found at various locations throughout the body, including the eyes, ears, mouth, digestive tract and vagina. Mucositis can reduce a child's quality of life by interfering with the ability to eat, or it can be life-threatening due to the development of an infection or an inability to proceed with cancer treatment. Genetic differences contribute to variability in drug response and the risk of developing side effects like mucositis. We have recruited 1835 children who have been treated with methotrexate, and I will uncover genetic characteristics that predict the likelihood of developing mucositis as a result of methotrexate. I will use this information to develop a predictive genetic test accompanied by clinical practice recommendations to help clinicians and patients better manage benefits and risks associated with methotrexate treatment. Knowing who is at higher risk prior to cancer treatment means that alternative treatment strategies can be considered, dosing can be adjusted in some cases, and monitoring for the development of mucositis can be enhanced. Ultimately, this work will allow for the incorporation of predictive genetic testing in childhood cancer treatment across Canada, an initiative already started in British Columbia, to improve the lives of children battling cancer.