Investigating the therapeutic potential of ATR-CHK1 axis inhibition in a neuroblastoma zebrafish larvae xenograft model

Michiels Thomas , 2022
Numerous children who survive cancer suffer from lifelong side effects as a result of chemotherapy. Chemotherapy kills both cancerous and healthy cells, the latter of which can have devastating effects on a child’s development, causing mental disabilities, organ toxicities, and secondary cancers. We tested a new therapy that aims to specifically target cancer cells in children with neuroblastoma, an aggressive cancer responsible for 15% of all cancer-related deaths in children. This treatment was tested on zebrafish larvae. In these larvae, we injected neuroblastoma cells that form a tumor. Then we gave the new therapy to the larvae to see if it could kill the cancer cells while sparing the healthy cells. We aimed to provide evidence for the new therapy and prove that we can test on zebrafish larvae how effective a cancer therapy can be. Hereby, zebrafish larvae can reduce the use of laboratory mice, which can have a significant economic benefit. In the future, we can inject patient-derived tumor cells into the larvae and test multiple treatments to determine the most effective therapy for each individual child, thereby improving the selection of cancer therapies and saving valuable time and money. We hope to help cure children with cancer without lifelong health problems, thereby improving their quality of life and giving them a better chance at a normal physical and social life. In the long run, this benefits our society economically by preventing the children we cure today from becoming the patients of the future.

Promotor Frank Speleman
Opleiding Biomedische Wetenschappen
Domein Medical Genetics