Drug combination for children with MYC amplified Medulloblastoma

Researchers discover drug combination that could offer a better prognosis for children diagnosed with MYC amplified Medulloblastoma, an often deadly form of brain cancer

Researchers at the University of Colorado Anschutz Medical Campus have found a drug combination that could offer a better prognosis for children diagnosed with MYC amplified Medulloblastoma.

Medulloblastoma is an often deadly form of brain cancer so this is welcome news to doctors and suffered alike.

“An oncogene called MYC is amplified in these tumors making them very susceptible to recurrence. In addition, there’s a greater risk of it spreading to other areas of the brain and down the spine,” said Siddhartha Mitra, PhD, assistant professor of Hematology-Oncology and Bone Marrow Transplant at the University of Colorado School of Medicine and University of Colorado Cancer Center member.

‘The five-year survival rate of this cancer is less than 45 percent’

“The five-year survival rate of this cancer is less than 45 percent. We wanted to discover better treatment options for these kids.”

Two drugs have already cleared phase I safety trials

The team discovered that two drugs which have already cleared phase I safety trials in other solid tumors. Together, they have a significant impact on these tumors which is promising news.

Using the epigenetic drug tacedinaline, the team found that in addition to making tumors grow, MYC was also hiding the tumors from the various immune cells in the body. They were able to unblock ‘don’t eat me pathways’ that prevent macrophages in the immune system from consuming a tumor and then made the tumor more enticing.

“When we used tacedinaline to unblock those pathways, and then added anti-CD47, a drug which makes macrophages become super eaters, the tumor became extremely appetizing to the macrophages enticing them to eat the tumor that was unblocked,” Mitra said.

‘You are essentially harnessing the body’s own immune system by giving it a jumpstart, much like a medical version of PacMan.’

“You are essentially harnessing the body’s own immune system by giving it a jumpstart, much like a medical version of PacMan.”

Targeting “pathway immune evasion pathways”

Mitra explained that while traditional therapies like chemotherapy have previously targeted the tumor growth pathways, this research is groundbreaking because it is the first time pathway immune evasion pathways are being targeted in these types of devastating brain tumors.

“Traditional adult cancer drugs don’t work well in kids because children are still developing and their normal cells divide at a rapid pace,” added Mitra.

“This drug combination could potentially help not only minimize the negative impacts of traditional cancer treatment in kids, but also give patients diagnosed with MYC amplified Medulloblastoma a better chance at survival.”

The next steps will be a clinical trial to determine the short and long-term effects of this treatment and, in addition to the Mitra lab, the Labs of Dr Sujatha Venkatraman and Professor Rajeev Vibhakar from CU-Anschutz will be involved.