Amit Bhavsar from University of Alberta and his colleagues have identified a receptor in cells that could be the key to preventing permanent hearing loss in childhood cancer survivors who are being treated with the drug Cisplatin. They believe that, by inhibiting this receptor, they may be able to reduce or eliminate the toxicity from the drug that causes hearing loss.
Cisplatin is an incredibly effective chemotherapeutic when it comes to treating solid tumors in children, contributing to an 80 percent overall survival rate over five years. Audiologists who work with patients undergoing Cisplatin therapy are all too familiar with the problem; nearly 100 percent of patients who receive higher doses show some degree of permanent hearing loss.
The receptor in question is Toll-like receptor 4 (TLR4), which is involved in the body’s immune response. It is a receptor that your body uses to detect when there is some sort of issue, like an infection. This receptor will turn on, and start producing signals that tell the cell it’s under stress. Unfortunately, in the case of Cisplatin, those signals ultimately lead to the death of the cells responsible for hearing.
The only way to prevent the damage is to stop the signals TLR4 produces that lead to the accumulation of Cisplatin. To confirm the efficacy of inhibiting the TLR4 receptor, Bhavsar and his team examined zebrafish sensory cells, which behave similarly to the hair cells in humans that are damaged by Cisplatin. Bhavsar was able to prove that inhibiting TLR4 led to an inhibition of the damage on the sensory cells.
Ghazal B, Asna L, Ivan K D, et al. (2021) Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity. EMBO Rep 22: e51280
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