Innovative drug combinations show potential treatment for deadly childhood cancer

Approximately 20 Australian children die each year from diffuse intrinsic bridge glioma (DIPG), an incurable brain tumor. The average age of DIPG diagnosis is only 7 years. There is no effective cure, and almost all children die of the disease, usually within a year of diagnosis.

Published in the prestigious journal Nature Communications on February 12, 2021, a potentially innovative drug that is “very effective in eradicating cancer cells” in animal studies and the world’s first 3D model of tumors. The combination of is revealed. David Ziegler, Principal Investigator and Associate Professor of Pediatric Oncologists, Children’s Cancer Institute and Sydney Children’s Hospital.

In preclinical studies of mouse models, researchers found that promising drug combinations led to the survival of two-thirds of mice, and drug combinations completed the growth of these highly aggressive tumors in these mice. I found that I would stop it.

Importantly, drug therapy, which is currently in early trials for adult cancer, is the most effective treatment ever tested in this incurable childhood cancer laboratory model. This treatment is a combination of two drugs, the established drug difluoromethylornithine (DFMO) and the investigational drug AMXT1501 being developed by Aminex Therapeutics.

DFMO is gaining increasing attention as a treatment for difficult-to-control cancers such as neuroblastoma, another advanced childhood cancer, and adult colorectal cancer. DFMO works by targeting the polyamine pathway, an important mechanism that enables tumor cell growth.

For the first time, Associate Professor Ziegler demonstrated that the polyamine pathway is important for DIPG cell proliferation. Ziegler and his team have developed Australia’s first DIPG research program using tumor cells donated by parents of a child who died of the disease.

From these, they created the first laboratory model of tumors to test new drugs. These models are used to show that DIPG can bypass DFMO activity by delivering polyamines into the cancer, essentially allowing tumors to continue to grow despite treatment with DFMO. They are now making the breakthrough discovery that treatment with the newly developed drug AMXT 1501 strongly blocks the transport of polyamines to DIPG cancer cells.

Treatment with AMXT 1501 was found to resensitize DIPG cells to DFMO, and Associate Professor Ziegler said, “It’s a stunning response in animal models, with significantly improved survival and minimal toxicity (side effects). It was. “

Associate Professor Ziegler said the drug combination clinical trials at DIPG are a global study led by the Children’s Cancer Institute and the Children’s Cancer Center at Sydney Children’s Hospital, which will begin this year in children. I said there is.

The Australian DIPG Tumor Database was launched in 2011 by the Children’s Cancer Institute. Australia’s first DIPG tumor database has helped Associate Professor Ziegler and his colleagues significantly contribute to the resolution of the disease. “Since establishing the Tumor Bank, we have been able to screen hundreds of drugs in the laboratory to find drugs that are effective in growing this highly aggressive cancer and killing cancer cells. Thanks to this ability, we are able to do it. Discover what we want to be the first effective treatment for DIPG. “

Rachael Gjorgjijoska was the first parent to agree to donate DIPG tumor tissue after her daughter Liliana died 15 months after diagnosis and only 4 years old.

I made the difficult decision to donate Liliana’s tumor because I wanted to make a difference. There was no cure to save Liliana from this catastrophic disease, but if her cancer cells helped advance research and there was a new cure for children in the future, this would be permanent for our little girl. It will be a typical memory. “

Rachael Gjorgjijoska, parent

Dr. Mark R. Burns, Founder, President and Chief Scientific Officer of Aminex Therapeutics and Inventor of AMXT1501, said: Overlapping findings for human cancer. We hope that this treatment will make a difference in the lives of DIPG and other patients with advanced cancer. “