Specific receptor in cells could serve as a key to prevent permanent hearing loss in childhood cancer survivors who are being treated with the drug cisplatin, as per a study "Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity," at the University Of Alberta Faculty Of Medicine & Dentistry, published in EMBO Reports.
Cisplatin is an incredibly effective chemotherapeutic when it comes to treating solid tumours in children, contributing to an 80 per cent overall survival rate over five years. But the problem is its side-effects of permanent hearing loss in nearly 100% of patients who receive higher doses of it.
It was stated that by inhibiting the receptor, they may be able to eliminate toxic side-effects from the drug that causes hearing loss.
Permanent Hearing Loss due to Cisplatin
The cells affected by TLR4's signals are located within the cochlea of the ear, where they play a crucial role in hearing, translating vibrations in the ear into electrical impulses. Cisplatin also accumulates in the kidneys, but the difference is that it can be flushed out and diluted in that area of the body; in a closed system such as the ear, it accumulates and damages the cells.
Hence stopping the signals produced from TLR4 that lead to the accumulation of cisplatin may help prevent the damage. The team thereby examined neuromasts, which are sensory cells within zebrafish that behave similarly to the human hair cells typically damaged by cisplatin.
The study proved that inhibiting TLR4 led to an inhibition of the damage on the sensory cells.
The team also works to refine an inhibitor that can disrupt this sampling process, removing the function that causes the toxic side-effect while still keeping the immune sensor function intact so patients don't become immunocompromised.
These findings thereby may help open the door for potential therapeutics in cancer and cisplatin-induced ototoxicity.