Funding outcome

Despite remarkable advances in developing new anti-cancer strategies, chemotherapy has remained one of the most effective treatments. Cisplatin is a highly potent chemotherapeutic agent widely used for treating solid tumors in adults and children; these include pediatric neuroblastoma, osteosarcoma, hepatoblastoma, brain tumors, and retinoblastoma. The major caveat of cisplatin is its various side effects, including neurotoxicity, nephrotoxicity, and ototoxicity. Cisplatin renders permanent and progressive bilateral high-frequency hearing loss that can expand to low frequencies, depending on the duration and doses of treatment. Although cisplatin-induced ototoxicity (CIO) occurs in more than 50% of patients, age is a significant risk factor as the incidence is higher among children, ranging from 22% to 70%. Hearing loss has a profound consequence in younger children; it impairs their neurocognitive abilities and psychosocial development. Therefore, developing effective treatments to prevent, or ameliorate the ototoxicity induced by cisplatin seems necessary. This research study will be done based on the inhibitors developed by our group at the University of Alberta. An infant murine inner ear cell line will be utilized as a relevant model for cisplatin cytotoxicity in children. This strategy will allow us to investigate the possible protective effects of these inhibitors on inner ear cells. Furthermore, these inhibitors will help us delve into underlying mechanisms and cellular pathways involved in CIO and find potent targets to reduce the hearing loss induced by cisplatin and eventually improve the overall health of children suffering from cancer.