Ewing sarcomas are very aggressive malignant tumors that occur mainly in children and adolescents. A team led by Martin Distel and Sarah Grissenberger of the St. Anna Children’s Cancer Research Center has now tested a number of active substances on zebrafish larvae that had previously been implanted with tumor cells from the child’s bone cancer. Certain drug combinations made the tumor smaller or even disappeared. They show an “Achilles heel” of this type of cancer.
Ewing’s sarcoma remains one of the most difficult childhood cancers to treat. The bone cancer in children is genetically well characterized, we already know the central protein that causes tumor growth in more than 85 percent of cases.
“But we still don’t know from which precursor or source cell the tumor arises. This makes drug testing more difficult,” cancer researcher Distel told the APA.
Zebrafish serves as ‘guinea pig’
The group presented the new method for particularly fast and efficient drug testing in the journal “Cancer Letters”. They used a model organism that has long proven to be a suitable helper in disease research: the zebrafish has a genetic makeup relatively similar to that of humans and is also transparent in the early stages of development, so that phenomena such as tumor growth and the effects of substances can be observed.
Researchers use “xenotransplantation” for approximation
They transplant human cancer cells into zebrafish larvae. Already after 24 hours of growth, the different active ingredients and combinations of active ingredients were added to the water of the fish. Analysis was performed after two days. Three promising drug combinations were found — “one of them was even able to completely kill the tumor cells in the zebrafish larvae,” Distel reported. The substances used activated the mechanism that should protect the organism against malfunctioning cells.
However, subsequent tests in mice have shown that the most effective combination of drugs “shows a certain toxicity in the mouse that was not shown in the fish,” said study co-author Distel. Due to the side effects, the active substance cannot be used in a concentration that completely eliminates the tumor.
Slows down tumor growth in the mouse model
“However, we were able to achieve concentrations in the mouse model without side effects slowing tumor growth,” said the researcher. “That’s how we discovered a specific Achilles’ heel of the tumor.” There are ideas and first approaches to not only inhibit, but completely break down the proteins responsible for tumor growth in a highly targeted way without damaging healthy cells.
Source: Krone
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