A Wayne State University researcher has received a $1.7 million, five-year award from the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health for the study, "Targeting nitrative stress for treatment of cisplatin ototoxicity." The research aims to address the critical gap that exists in understanding how nitrative stress caused by cisplatin treatment alters cochlear protein signaling causing apoptosis – or death of cells – in cisplatin-induced ototoxicity.
The study, led by Samson Jamesdaniel, Ph.D., assistant professor of family medicine and public health in Wayne State's School of Medicine and in the Institute of Environmental Health Sciences, stated that cisplatin and its analogs are prescribed to 10 to 20% of all cancer patients, causing hearing loss in up to 80% treated with the drug.
"Cisplatin is a first-generation platinum-based anti-neoplastic drug that is the backbone of combination therapies to treat cancers of the bladder, cervix, lung [non-small cell], head and neck [squamous cell], testicle, mesothelium and some other solid tumors," said Jamesdaniel. "The ototoxicity caused by treatments using cisplatin can significantly affect the quality of life in cancer survivors and lead to devastating consequences in children, with impacts on speech and language development, education and social integration."
Cisplatin-induced nitration and downregulation of LMO4, a molecular adaptor protein, appears to mediate its ototoxic effects. Jamesdaniel and his research team hope to better understand the characterization of the regulatory role of LMO4 nitration in cisplatin-mediated ototoxicity that may reveal the biological significance of this novel molecular mechanism.
The outcomes of this research will have important translational value by providing a strong foundation for identifying and developing novel therapeutic approaches to prevent the ototoxic effects of cisplatin. Samson's important research may lead to an effective intervention for cisplatin-induced ototoxicity that will improve lives of cancer survivors who have received this treatment."
Timothy Stemmler, Ph.D., interim vice president for research, Wayne State
The project number for this National Institutes of Health study is DC020299.