Funding outcome

Over the last sixty years, survival rates for childhood cancer treatments have steadily increased and now approach 80% overall. Over the last twenty years it has become widely appreciated that survivors of childhood cancer are at risk of serious health complications. Cisplatin is an anticancer drug that is frequently used to treat solid tumours in children because it is highly effective. Unfortunately, cisplatin treatment frequently results in severe side effects that include kidney damage, nerve damage and permanent hearing loss. The latter is a burden in children that are developing speech and language skills. It has also been shown that socio-economic status in later life is affected by this hearing loss indicating that cisplatin hearing loss has serious impacts on the quality of life in cancer survivors. We believe that being able to predict who will suffer from cisplatin-induced hearing loss, or developing therapies that specifically prevent hearing loss, will improve the quality of life of childhood cancer survivors. We have examined whether a patient's genetics influences their risk of developing cisplatin hearing loss. We found that a gene in the immune system was contributing to cisplatin hearing loss. In this project we aim to confirm that finding by assessing whether cells that lack this gene respond differently to cisplatin, compared to cells that contain this gene. If we observe differences in cisplatin responses between these cells we will be able to justify targeting this gene to develop preventative therapies against cisplatin hearing loss. We will begin by designing a cell line that lacks this gene and test its absence at the genetic and protein levels. We will also examine cell responses that are known to depend on the gene to confirm its absence. This deleted cell line will be a valuable tool for future studies that examine the role of innate immune signaling in cisplatin hearing loss.