广泛使用的化疗顺铂会导致 40-60% 的癌症患者永久性听力损失。 FDA 批准一种药物硫代硫酸钠用于患有局部实体瘤的儿科患者，以预防顺铂引起的听力损失，但迫切需要更多的药物。在这里，我们在临床相关的多剂量顺铂小鼠模型中测试了达拉非尼（FDA 批准的 BRAF 激酶抑制剂和抗癌药物）。达拉非尼与顺铂每日口服两次，其保护作用通过功能性听力测试和耳蜗外毛细胞计数来确定。评估药物联合治疗的毒性，并测量 pERK 水平。达拉非尼（Dabrafenib）的剂量为 3 mg/kg/bw，每天两次，在小鼠中被确定为最低有效剂量，相当于 FDA 批准的人类癌症治疗每日剂量的十分之一。雌性和雄性小鼠在三个测试频率下获得的听力保护水平在治疗完成后持续了四个月，均为 20-25 dB。此外，达拉非尼在两种不同的小鼠品系中表现出良好的体内治疗指数（> 25）、听力保护以及减少顺铂引起的体重减轻。总而言之，这项研究表明达拉非尼是一种有前途的预防顺铂引起的听力损失的候选药物。

The widely used chemotherapy cisplatin causes permanent hearing loss in 40-60% of cancer patients. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multi-dose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cells counts. Toxicity of the drugs co-treatment was evaluated, and levels of pERK were measured. Dabrafenib, in dose of 3 mg/kg/bw, twice daily, in mice, was determined to be the minimum effective dose and it is equivalent to one tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20-25 dB at the three frequencies tested, in both female and male mice, persisted for four months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), hearing protection in two different mouse strains, and diminished cisplatin-induced weight loss. Altogether, this study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss.