A study led by researchers at Children’s Cancer Institute has uncovered a potential new therapeutic approach for neuroblastoma, the most common tumour in children under five, and possibly some other cancers as well.
Published in the Journal of Proceedings of the National Academy of Sciences USA, the study identified and tested a new targeted therapy, finding that it not only reduced the growth of neuroblastoma cells in culture, but also significantly extended survival in mice with neuroblastoma.
“Children with high-risk neuroblastoma, the really aggressive subtypes of this disease, go through very intensive treatment,” said Professor Murray Norris AM, senior author on the paper. “Only about 50% of these kids make it through, and those who survive are left with serious long-term health problems because of the toxicity of the treatments given. We want to find a new way of treating this disease that is not just effective, but also much safer to use in children.”
About half of all children with high-risk neuroblastoma are found to have increased copies of a gene known as the MYCN oncogene. MYCN is well-recognised as a key driver of this disease, as well as several other childhood cancers including medulloblastoma, Wilms tumor and retinoblastoma. Despite this, scientists have so far been unsuccessful in developing a drug that successfully targets the MYCN oncogene, nullifying its effects. Now, for the first time, researchers appear to have found a drug capable of doing just that — a small molecule inhibitor known as M606.
“M606 acts as an iron chelator, which is a drug that binds to iron molecules inside the body,” explained Professor Norris. “Fast-growing neuroblastoma cells have a strong dependency on iron, far greater than normal cells, and removing iron from these cells seriously interferes with their growth. Unlike other iron chelators developed in the past, M606 is able to not only remove iron from the blood, but also from within the cancer cells themselves, where iron is stored.”
The study’s results showed that M606 is able to selectively target neuroblastoma cells expressing high MYCN levels, reducing cell proliferation and killing many of the cells. In a living model of neuroblastoma, mice specially bred to grow human neuroblastoma cells, the study found that M606 delayed tumour development and significantly extended survival.
“These very promising results suggest that M606 could have significant potential as a new anti-cancer treatment,” commented Professor Norris. “There is now further research that needs to be done, including testing the effects of M606 when used in combination with other therapeutic agents. Should this research be successful, we hope to see this agent reach clinical trial and, in the future, make a real difference for children with neuroblastoma.”
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