Strategies to reduce the risk of platinum containing antineoplastic drug-induced ototoxicity
| Autor: | Debashree Mukherjea, Katlyn Woolford, Vickram Ramkumar, Priyanka Bhandari, Jacob Franke, Amit Sapra, Leonard P. Rybak, Asmita Dhukhwa |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Hearing loss Antineoplastic drug Antineoplastic Agents Platinum Compounds Toxicology Protective Agents 030226 pharmacology & pharmacy Article 03 medical and health sciences 0302 clinical medicine Ototoxicity Internal medicine Neoplasms medicine otorhinolaryngologic diseases Animals Humans Child Hearing Loss Cochlea Pharmacology Cisplatin business.industry General Medicine medicine.disease Clinical trial 030220 oncology & carcinogenesis Quality of Life medicine.symptom business Reactive Oxygen Species medicine.drug |
| Zdroj: | Expert Opin Drug Metab Toxicol |
| ISSN: | 1744-7607 |
| Popis: | INTRODUCTION: Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer permanent sensorineural hearing loss. Up to 60% of children and at least 50% of adults suffer this complication that seriously compromises their quality of life. Hearing loss is due to damage to the sensory cells in the inner ear, primarily the outer hair cells and cells of the stria vascularis and spiral ganglion. The mechanisms of cochlear damage are still being investigated. However, it appears that most damage to the inner ear is triggered by reactive oxygen species (ROS) formation and inflammation. AREAS COVERED: In this review we discuss a number of potential therapeutic targets that can be addressed to provide hearing protection. These strategies include enhancing the endogenous antioxidant pathways, heat shock proteins, G protein coupled receptors and counteracting enzymes that produce ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1. EXPERT OPINION: A number of potential protective agents show promise in animal models by systemic or local administration by transtympanic or intracochlear injection. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate administration in two studies of pediatric tumors. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|