Each year around 20 Australian children die from the intractable brain tumor, Diffuse Intrinsic Pontine Glioma (DIPG). The average age of diagnosis for DIPG is just seven years. There are no effective treatments, and almost all children die from the disease, usually within a year of being diagnosed.
A paper published today 12 February 2021 in the prestigious journal Nature Communications reveals a potentially revolutionary drug combination – in animal studies and in 3D models of the tumor at the first stage in the world. -world – “highly effective in eradicating cancer cells,” says lead researcher and pediatric oncologist Professor David Ziegler, of the Children’s Cancer Institute and Sydney Children’s Hospital.
In preclinical trials in mouse models, the researchers found that the promising combination of drugs caused survival in two-thirds of the mice and that the drug combination completely stopped the growth of the aggressive tumors. that in those mice.
Importantly, the therapy drug, currently in early trials in adult cancer, is the most effective treatment ever tested in laboratory models of this infertile childhood cancer. The treatment is a combination of two drugs: difluoromethylornithine (DFMO), an established drug, and AMXT 1501, a research agent being developed by Aminex Therapeutics.
The DFMO is gaining increasing attention as a treatment for difficult-to-control cancers such as neuroblastoma, other invasive childhood cancers, and colorectal cancers in adults. DFMO works by targeting the polyamine pathway – an important mechanism that allows tumor cells to grow.
Professional 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 research program into DIPG using tumor cells donated by parents of children who have died from the disease.
From these, they created the first laboratory models of the eardrum to try new drugs. These models were used to show that DIPG can inhibit DFMO activity by pumping polyamines to cancer, essentially allowing the eardrum to continue to grow despite treatment with DFMO. They have now found that treatment with a new developmental drug, AMXT 1501, strongly inhibits the transport of polyamines into the DIPG cancer cell.
Treatment with AMXT 1501 was found to reactivate the DIPG cells to DFMO leading to what Professional Professor Ziegler said, “it was a remarkable response in animal models, with much greater survival and minimal toxicity (side effects) “.
Professor Ziegler said clinical trials of the drug mix in DIPG are set to begin this year in children in a global study led by the Children’s Cancer Institute and the Children’s Cancer Center at Sydney Children’s Hospital.
The Australian DIPG Tumor Database was started by the Children’s Cancer Institute in 2011. Australia’s first DIPG tumor database has allowed Professional Professor Ziegler and his colleagues to make significant progress in resolving on this disease. “Since we set up the tumor bank we have been able to grow this highly invasive cancer in our labs to allow us to screen hundreds of drugs to find those that are effective in killing the cancer cells. It is because of this ability that we have been able to find out what we hope will be the first effective treatment for DIPG, “he said.
Rachael Gjorgjijoska was the first parent to agree to donate a DIPG tumor after the death of her daughter Liliana at just 4 years, 15 months after her diagnosis.
We made the difficult decision to donate Liliana tumor because we wanted to make a difference, there were no cures to save Liliana from this devastating disease, but if her cancer cells help research so there will be new treatments for her children in the future, this will make you a lasting memory of our little girl. “
Rachael Gjorgjijoska, Parent
Dr Mark R. Burns, Founder, President and Chief Scientific Officer of Aminex Therapeutics, and engineer of AMXT 1501, said “the remarkable results against this devastating disease shown by Dr Ziegler and his team are contributing more fire to our motivation to see these. results doubled against human cancers. We hope that this treatment will make a difference in the lives of those with DIPG and other invasive cancers. “
Source:
Australian Children’s Cancer Institute