NIH study uncovers clues about why common cancer drug causes hearing loss

Researchers find target to protect hearing during chemotherapy treatment.

Cisplatin and similar platinum-based drugs are prescribed for an estimated 10-20% of all cancer patients. The NIH’s National Cancer Institute supported research that led to the 1965 discovery of cisplatin and continued development leading to its success as an essential weapon in the battle against cancer. The drugs cause permanent hearing loss in 40-80% of adult patients and at least half of children who receive the drug. The new findings help explain why cisplatin is so toxic to the inner ear, and why hearing loss gets worse after each treatment, can occur long after treatment, and is more severe in children than adults.

In most areas of the body, cisplatin is eliminated within days or weeks after treatment, but in the inner ear, the drug remains much longer. Previous research focused on why the inner ear is more sensitive than other parts of the body to cisplatin-induced damage. The NIH team pursued a new angle on the problem: What if the inner ear is not able to get rid of cisplatin, and cells in the inner ear important for hearing die because they are exposed to the drug for a long time?

The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients. By looking at inner ear tissue of mice after the first, second, and third cisplatin treatment, researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues, and that it builds up with each successive treatment. They also studied inner ear tissue donated by deceased adult patients who had been treated with cisplatin, and observed that cisplatin is retained in the inner ear many months or years after treatment. In addition, when they examined inner ear tissue from one child, they found cisplatin buildup that was even higher than seen in adults. These results suggest that the inner ear readily takes up cisplatin, but it has very little ability to remove the drug.

In mice and human tissues, the research team saw the highest buildup of cisplatin in a part of the inner ear called the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound. The research team determined that the accumulation of cisplatin in the stria vascularis portion of the inner ear contributed to cisplatin-related hearing loss.

“Our findings suggest that if we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment, we may be able to protect cancer patients from developing cisplatin-induced hearing loss,” said Cunningham.

The study, published in Nature Communications), was supported by the National Institute on Deafness and other Communications Disorders (NIDCD), part of the National Institutes of Health.

Lisa L. Cunningham, chief of the NIDCD Section on Sensory Cell Biology, led the research team, which included scientists from the National Institute on Minority Health and Health Disparities (NIMHD) and the National Center for Advancing Translational Sciences (NCATS). Support for data analysis was provided by Electro Scientific Industries of Bozeman, Montana.