Medulloblastoma is the most common malignant brain tumour in children, and few good treatment options exist. Now researchers at Fox Chase Cancer Center have found a promising new approach using a drug that’s already being used to treat hypothyroidism.

In a mouse study, they showed that the drug, T3, fought cancer in a surprising way: by preventing developing tumour cells from becoming cancerous and causing them to become normal cells instead. It’s a novel and potentially less toxic approach to treatment than the powerful chemotherapies that are currently in use.

They presented their research today at the American Association for Cancer Research Annual Meeting 2023 at the Orange County Convention Center in Orlando, Florida.

“A big flaw of the current treatment is that it causes significant toxicity,” saidZeng-jie Yang, MD, PhD, an associate professor in the Nuclear Dynamics and Cancer research program at Fox Chase and lead author on the study. “We really need better treatment options that are a more effective and less toxic approach to treating these tumours.” Yijun “Boris” Yang, PhD, a postdoctoral associate in Zeng-jie Yang’s lab, conducted much of the work and was a co-author of the study.

Even with the current treatment approach of chemotherapy and radiation therapy, many patients with medulloblastoma still die from the disease. Those who survive are often left with lifelong side effects, including cognitive deficits and endocrine disorders, that negatively affect their quality of life.

For the new study, researchers wanted to look at the relationship between medulloblastoma and thyroid hormone. It was already known that many medulloblastoma patients had low levels of thyroid hormone and that lower levels were linked to poorer outcomes. But it was generally thought that this hypothyroidism was caused by chemotherapy or radiation therapy.

In the study, they treated mice that had medulloblastoma with T3, a synthetic form of the thyroid hormone triiodothyronine, which is often used to treat hypothyroidism. “Surprisingly, the treatment dramatically inhibited tumour growth,” Zeng-jie Yang said.

When researchers looked more closely at what was happening, they saw that the drug was not attacking and killing cancer cells like conventional chemotherapies. Rather, it was preventing cells from becoming cancerous at all.

This occurs through a process called “terminal differentiation.” As the cell is developing, at the final stage that determines what kind of cell it is going to be, it changes to become a normal cell instead of cancerous.

“In other words,” Zeng-jie Yang said, “it can be reprogrammed to undergo normal differentiation.” A major focus of Yang’s lab is understanding the differentiation process for cancer cells and how it can be normalised.

“In this study, we not only demonstrated the mechanism for the terminal differentiation of the tumour cells, but we also proved that we can use an established drug to induce the tumour cell differentiation, thereby treating medulloblastoma.”

This type of “differentiation therapy” is a promising new treatment for some leukaemias, but has not yet been tried for this type of cancer, he noted.

The fact that they were able to demonstrate effectiveness in a drug that’s already approved by the Food and Drug Administration is key, because it can significantly reduce the time needed to make a potential new therapy available, he added.

Next, the team hopes to move toward a clinical trial in partnership with paediatric hospitals. They’re also investigating a potential combination treatment of T3 and chemotherapy.

“In the long term, we plan to move to another brain tumour, glioblastoma, which is a malignant brain tumour in adults,” he said. “We’re trying to study the mechanism for terminal differentiation in these tumours.”

The study, “Thyroid Hormone Drives the Terminal Differentiation of Tumor Cells in Medulloblastoma,” was presented by Yijun “Boris” Yang during a poster session.

Source: Fox Chase Cancer Center