Cisplatin chemotherapy is widely used in the treatment of pediatric cancers, but it also causes both hearing loss (ototoxicity) and nerve damage (neuopathy) in a high percentage of treated patients. The cellular mechanisms underlying these pathologies are poorly understood. Our studies will use novel zebrafish models of ototoxicity and sensory neuropathy to address the following three aims:
Proposed specific aims
· Determine whether the circadian clock within sensory cells influences their susceptibility to cisplatin.
· Establish whether pre- or co-treatment with the corticosteroid dexamethasone can reduce sensory pathology caused by cisplatin.
· Perform a high-throughput screen of FDA approved drugs and bioactive compounds aimed at identifying small molecules that can either prevent or reverse neuronal damage caused by cisplatin.
Potential impact on child health
The results could lead to improved approaches to reduce and/or treat ototoxicity and nerve damage in children undergoing chemotherapy with cisplatin.