New Therapeutic Approach to Fight Pediatric Cancer


The most common type of solid tumor affecting young children is neuroblastoma.  It develops from immature nerve cells, typically in the adrenal glands, but can also originate within the neck, chest, abdomen or spine.  Symptoms include fever, pain throughout the body, lumps of tissue swelling under the skin and dark blemishes.  On top of the physical manifestation of the disease and the heavy chemo treatment, patients who are often 5 or younger also have to deal with the psychological impact of their situation.

A team of Australian researchers from the Children’s Cancer Institute is hoping to bring some much-needed relief to patients with neuroblastoma.  Their latest investigation revealed a crucial link between a cancer-causing gene and a group of molecules that help cells grow.

The MYCN oncogene has been strongly associated with solid tumor and frequently appears in neuroblastoma cases.  While there are no current ways of dealing with the gene, the team focused on indirect ways of interfering with its activity.  They noticed that polyamines, organic compounds that fuel the growth and survival of cancer cells, are entirely regulated by the MYCN oncogene.  Having the knowledge that MYCN controls polyamine levels in cancer cells means that scientists for the first time have a potential therapeutic “way in” to disrupting cancer cell growth.

This exciting new treatment approach warrants clinical investigation in children with MYCN-driven high-risk neuroblastoma, and potentially other cancers as well”, explained Professor Michelle 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”.

In their recent study, they explain how an inhibitor drug called AMXT-1501 can be used gene to block the gene responsible for the uptake of polyamines by neuroblastoma cells.  Combining Difluoromethylornithine (DFMO) and AMXT-1501 with conventional chemotherapy managed to significantly increase survival in mouse models and prevent tumor formation.

These results are very exciting and offer a new and potent way to target childhood cancers”, added Associate Professor David Ziegler, pediatric oncologist at the Sydney Children’s Hospital.  “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”.