Researchers discover potential new treatment for deadly childhood brain cancer

Washington: Each year, around 20 Australian children die from the incurable brain tumor, diffuse pontine intrinsic glioma (DIPG). The average age of diagnosis of DIPG is only seven years. There is no effective treatment and almost all children die from the disease, usually within a year of diagnosis.

An article published in the journal Nature Communications reveals a potential combination of breakthrough drugs which – in animal studies and in the world’s first 3D models of the tumor – is “spectacularly effective in eradicating cancer cells”, according to the principal investigator and pediatrician . oncologist associate professor c at the Children’s Cancer Institute and Sydney Children’s Hospital.

In preclinical trials on mouse models, the researchers found that the promising drug combination led to the survival of two-thirds of the mice and that the drug combination completely stopped the growth of these very aggressive tumors in these mice.

Importantly, drug therapy, which is currently being tested early in adult cancer, is the most effective treatment ever tested in laboratory models of this incurable childhood cancer. Treatment is a combination of two drugs: difluoromethylornithine (DFMO), an established drug, and AMXT 1501, an investigational agent developed by Aminex Therapeutics.

DFMO is gaining more and more attention as a treatment for hard-to-control cancers like neuroblastoma, another aggressive cancer in childhood, and colorectal cancer in adults. DFMO works by targeting the polyamine pathway – an important mechanism that allows tumor cells to grow.

Associate Professor Ziegler has shown for the first time that the polyamine pathway is essential for the growth of DIPG cells. Ziegler and his team developed Australia’s first DIPG research program using tumor cells donated by parents of children who died of the disease. From these, they created the first laboratory models of the tumor to test new drugs.

These models were used to show that DIPG can bypass DFMO activity by pumping polyamines into the cancer, essentially allowing the tumor to continue to grow despite treatment with DFMO. They have now made the breakthrough discovery that treatment with a new developmental drug, AMXT 1501, potently blocks the transport of polyamines into the DIPG cancer cell. Treatment with AMXT 1501 was found to resensitize DIPG cells to DFMO leading to what Associate Professor Ziegler said, “was a dramatic response in animal models, with significantly increased survival and minimal toxicity (side effects). “

Associate Professor Ziegler said clinical trials of the drug combination in DIPG are expected to begin this year in children as part of a global study by the Children’s Cancer Institute and the Children’s Hospital Kid’s Cancer Center. from Sydney.

The Australian DIPG Tumor Database was launched by the Children’s Cancer Institute in 2011. Australia’s first DIPG Tumor Database has enabled Associate Professor Ziegler and colleagues to make great strides in solving this problem. disease. “Since the inception of the tumor bank, we have been able to develop this very aggressive cancer in our laboratories to allow us to screen hundreds of drugs to find those that are effective in killing cancer cells. It is with this ability that we were able to discover what we hope will be the first effective treatment for DIPG, ”he said.

Rachael Gjorgjijoska was the first parent to agree to donate DIPG tumor tissue after the death of her daughter Liliana at just 4 years old, 15 months after her diagnosis. Rachael comments “We made the difficult decision to donate Liliana’s tumor because we wanted to make a difference, there was no treatment to save Liliana from this devastating disease, but if her cancer cells help advance research, so there will be new treatments for children in the future., it will be a lasting memory of our little girl. “

Dr Mark R. Burns, Founder, Chairman and Scientific Director of Aminex Therapeutics, and inventor of AMXT 1501, said that “the dramatic results against this devastating disease demonstrated by Dr Ziegler and his team add greater fire to our motivation to see these results duplicated against human cancers. We hope this treatment will make a difference in the lives of people with DIPG and other aggressive cancers. “

This work was supported by grants from the National Health and Medical Research Council, Cancer Institute NSW, DIPG Collaborative, Cure Starts Now, Cure Brain Cancer Foundation, The Levi’s Project, Benny Wills Brain Tumor Research fund, du Tour de Cure, Isabella and Marcus Gemma Howell Foundation Scholarship and Aminex Therapeutics, Inc.