Scientists discover potential way to treat and prevent neuroblastoma in children

Scientists discover potential way to treat and prevent neuroblastoma in children

The MYCN oncogene has long been known to be a key cause of a number of deadly solid tumour cancers, including neuroblastoma, which claims more lives of children under the age of 5 than any other cancer.

Neuroblastoma is the most common solid tumour found in young children.

In up to 25% of cases, the tumours contain an increased number of copies of MYCN, and children with these ‘high-risk’ neuroblastomas have a particularly poor prognosis.

To date, no drugs have been able to directly target MYCN, so scientists have looked at other ways to halt the progress of neuroblastoma.

One group of target molecules, known as polyamines, are known to be critical for cell growth and survival and are present in high concentrations in cancer cells.

However, clinical trials of agents that target the polyamine pathway have proven disappointing.

In a study published in Science Translational Medicine, researches have uncovered a previously unknown and crucial link between polyamines and MYCN, revealing that the polyamine pathway is entirely regulated by the MYCN oncogene.

The discovery of this link – by which MYCN controls polyamine levels in cancer cells, driving the growth and proliferation of the neuroblastoma cells is meaningful as scientists have a potential therapeutic “way in” to disrupting cancer cell growth for the first time.

Previously, the research team have shown that a drug called DFMO is able to target a gene involved in the synthesis of polyamines.

There is currently a clinical trial underway at the Kids Cancer Centre, Sydney Children’s Hospital, and in 14 leading US children’s cancer centres, to study the use of DFMO when given with existing anti-cancer drugs, to treat children with relapsed neuroblastoma.

In the current study, researchers have identified the gene responsible for the uptake of polyamines by neuroblastoma cells and have demonstrated that this gene can be inhibited using a drug called AMXT-1501.

By combining these two drugs, DFMO and AMXT-1501, with conventional chemotherapy, the research team were able to significantly increase survival in mice with established neuroblastoma tumours, as well as prevent tumour formation in mice who were tumour-free but genetically prone to developing the disease.

The newly discovered combination therapy is currently in Phase 1 clinical trials and is being tested in adult patients with a broad range of cancers in the US.

“This exciting new treatment approach warrants clinical investigation in children with MYCN-driven high-risk neuroblastoma and potentially other cancers as well,” said Haber. “While other treatment approaches in clinical evaluation are designed to inhibit polyamine synthesis, they do not impact polyamine uptake from the microenvironment. Our study suggests that both polyamine synthesis and polyamine uptake need to be inhibited for therapy to be effective.”

Mark Burns, an author on the paper described the study’s results as “impressive” and said they further bolster excitement about the potential for polyamine depletion therapy as a new treatment approach.

“These findings demonstrate the benefit of combining inhibition of polyamine synthesis with blockade of polyamine transport and suggest that combining AMXT 1501 and DFMO with standard chemotherapy may be a potent treatment strategy for high-risk neuroblastoma patients,” Burns said.

“These results are very exciting and offer a new and potent way to target childhood cancers,” said David Ziegler, leader of the clinical trial. “We have already shown in our current clinical trial that targeting polyamines with one drug (DFMO) can be safely achieved in combination with chemotherapy. By combining two drugs targeting the same pathway we have the potential to further improve the anti-cancer effect for these children. We are now working to develop a children’s formulation of AMXT-1501 and once the initial adult trial is complete, we plan to open a clinical trial for children with the most aggressive cancers.”

Source: and Children’s Cancer Institute Australia

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