Neuroblastoma is a childhood cancer that can go into remission on its own. Now, researchers have identified a possible reason why and used the underlying mechanism to treat tumours in mice
28 April 2022
Certain types of neuroblastoma, a nervous system cancer mostly found in children, have cells that rely on an amino acid to evade the immune system’s attempts to destroy them. Suppressing the production of this amino acid in mice led to a reduction in tumour sizes and remission of the cancer — a technique that could be used in future human trials.
Andrés Flórez at Harvard University and Hamed Alborzinia at the German Cancer Research Center analysed cultured tumour cells of a particularly aggressive type of neuroblastoma. This form has abnormal expressions of the gene MYCN, which causes cells to consume large amounts of iron. This mineral is necessary for cell growth and proliferation, but, in excess, it can damage cell membranes and induce cell death – a process known as ferroptosis.
Flórez and his colleagues found that these neuroblastoma cells evaded the process with the help of an amino acid called cysteine.
“Cysteine actually protects the cells from all this damage, and when we take it out of the cells, they become extremely sensitive to ferroptosis,” says Flórez. “The cells died massively, but only the cells that had this gene MYCN.”
Mice treated with two drugs that suppress the production of cysteine had a 60 per cent reduction in tumour growth compared with a control group that was given no treatment. The group given the drugs also had no apparent side effects. By pairing this drug cocktail with a third intervention targeting a gene responsible for cell membrane repair, the team saw complete tumour remission after 14 days in 10 out of 12 mice and significant reductions in tumour size in the other two.
Neuroblastoma is one of the most common cancers to spontaneously resolve on its own, a phenomenon mostly seen in children under 18 months old. “These [findings] could absolutely help explain this phenomenon,” says Julie Krystal at the Cohen Children’s Medical Center in New York. More research would need to be done to test the hypothesis, but Flórez says that this age group tends to have lower cysteine levels.
While the three-pronged treatment still needs to be optimised before it can be used in human clinical trials, Flórez is hopeful it will open the door to treating other aggressive forms of cancer, too.
“Neuroblastoma is a tumour in children, so it’s very specific,” says Flórez. “Our goal is to translate this therapy into other tumours that are more frequent in adults, like lung cancer and breast cancer, that also have this [abnormal] gene MYCN.”
Journal reference: Nature Cancer, DOI: 10.1038/s43018-022-00355-4
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