Improving the quality of life for childhood cancer survivors

New research offers insight into genetic variants that influence drug responses

Ghazal Babolmorad Half of all children treated with a common chemotherapy drug lose their hearing permanently, but University of Alberta research offers insight into how genes affect a person’s response to drugs—potentially leading to effective and safe doses tailored to each child’s genetic makeup.

“Hearing loss in young children can have significant lifelong consequences by affecting the development of speech, language and social skills, as well as increasing the risk of learning difficulties,” said Ghazal Babolmorad, a third-year PhD student in the Department of Medical Microbiology and Immunology, who is focusing her research on the mechanism behind why exactly 40 to 60 per cent of children treated with a chemotherapy drug develop permanent, bilateral hearing loss by examining the immune responses to the drug.

She said while cisplatin, a platinum-based chemotherapy drug, is among the most effective against solid tumours and is widely prescribed to children with brain, liver and bone cancer, it also leaves 90 per cent of children treated with side effects, which besides hearing loss include kidney damage and heart damage.

Babolmorad explained the platinum atom at the centre of cisplatin is responsible for killing the cancer cell, but can also cause inflammation in the cochlea, resulting in damage to the auditory cells and hearing loss. But the mechanisms behind this inflammation aren’t clear.

She identified that platinum, and cisplatin by extension, can activate an immune receptor usually found on a cell membrane that causes a response in the immune system—like inflammation in the cochlea.

However, thanks to genetic variation, there are people who express a low level of this immune receptor, called TLR4, which means their immune system isn’t activated and they have a low-risk of developing hearing loss, said Babolmorad, who recently posted her findings in bioRxiv, an open-access preprint repository.

Now, Babolmorad is working with other U of A researchers to examine potential synthetic inhibitors that can block the TLR4 receptor—minimizing an immune response and preventing this devastating hearing loss.

“If we’re able to make cisplatin, an otherwise invaluable chemotherapeutic tool, safe for everyone—not just low-risk patients—it could be a game-changer for the quality of life of the children using cisplatin as their cancer therapy.”

Ghazal Babolmorad is supervised by Amit Bhavsar. Her Graduate Studentship project is funded by the Stollery Children’s Hospital Foundation through WCHRI.

 

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