Newly discovered chemical compound suggests potential treatment of childhood cancer
Researchers at IGP have identified a molecule that could be used as a new treatment strategy for the pediatric cancer types neuroblastoma and medulloblastoma. This is shown in a recent paper published in the journal Cell Death and Disease.
Neuroblastoma and medulloblastoma are among the most severe pediatric tumours. Current therapies are not always effective, and disease relapses are relatively common. There is therefore an urgent need to identify new proteins in the cancer cells that can work as druggable targets.
In the current study, the researchers identified the chemical substance FLIX5 with great toxicity towards both neuroblastoma and medulloblastoma cells.
“We identified FLIX5 when we screened almost 1600 chemical substances in multiple cancer cell models. FLIX5 was particularly interesting since its toxicity was specific towards cancer cells, affecting normal cells much less. In addition, we showed that FLIX5 was effective not only against actively proliferating cancer cells, but also against the dormant and chemo resistant cell population. This is very important since these cells are thought to result in relapse,” says Emma Lindell, doctoral student at IGP and first author of the study.
When the researchers studied the toxic effect in more detail, they found that in neuroblastoma cells, FLIX5 targets the protein EPLIN which leads to controlled cell death, apoptosis. The potential reason for this appears to be EPLIN’s role in binding to cells structures required for cell division and cell motility. Through EPLIN, FLIX5 also affects lipid metabolism and the function of mitochondria, the cells’ energy producing structures.
“Another interesting result was that FLIX5 acts synergistically with two drugs that are used in standard treatment of care in neuroblastoma. When they were combined with FLIX5 the cancer cells showed a reduced survival compared to when they were used separately,” says Emma Lindell.
“In summary, our study shows that EPLIN has the potential as a new druggable target in neuroblastoma and we think it might have a similar role in medulloblastoma. This presents new opportunities for treating these severe diseases, and potentially also other tumour types,” says Xiaonan Zhang, researcher at IGP, who has led the study.