The new drug combination could be effective in treating often fatal childhood brain tumors

Researchers at the University of Colorado's Anschutz School of Medicine have discovered a combination of drugs that may provide a better prognosis for children diagnosed with MYC enlarged into medulloblastoma, a commonly fatal brain cancer
.
The study was carried out
in cooperation with the University Hospital of Düsseldorf of the German Cancer Alliance (DKTK).

"An oncogene called MYC is amplified in these tumors, making them very susceptible to recurrence
.
In addition, there is a greater risk of it spreading to other areas of the brain and spine," said
Dr.
Siddhartha Mitra, assistant professor of hematology-oncology and bone marrow transplantation at the University of Colorado School of Medicine and a member of the University of Colorado Cancer Center.
"The five-year survival rate for this cancer is less than 45 percent
.
We want to find better treatment options
for these children.
”

Mitra's team found that two drugs that had passed phase I safety trials in other solid tumors had a significant effect
on these tumors when combined.

Using the epigenetic drug tadenaline, the team found that MYC, in addition to making tumors grow, also hide tumors from various immune cells in the body
.
They were able to lift the so-called "don't eat me pathway" and stop macrophages in the immune system from engulfing tumors
.

Then they make the tumor more attractive
.

"When we used tadinarine to unlock these pathways and then added anti-CD47 [a drug that makes macrophages super eaters], the tumors became very attractive to macrophages, inducing them to eat the unlocked tumors
.
" "You're basically harnessing the body's own immune system and getting it to spin up quickly, like the medical version of Pac-Man
.
"

Mitra, who is also part of the Center for Cancer and Blood Disorders at Children's Hospital of Colorado, said that while traditional therapies such as chemotherapy have previously targeted tumor growth pathways, this is the first time immune evasion pathways have targeted such devastating brain tumors
.

"Traditional adult cancer drugs don't work well in children because children are still developing and their normal cells divide quickly
.
" "This combination of drugs may not only help minimize the negative effects of traditional cancer treatments on children, but may also provide a better chance
of survival for patients diagnosed with MYC-amplified medulloblastoma.
"

The next step, he said, will be clinical trials to determine the short- and long-term effects
of this treatment.
In addition to Mitra's lab, the labs of Dr.
Sujatha Venkatraman and Prof.
Rajeev Vibhakar from Anshutz University were also involved in the research
.