Researchers from Fox Chase Cancer Center have identified a widely used thyroid hormone that may significantly improve treatment outcomes for medulloblastoma, the most common malignant brain tumor in children. The study found that adding triiodothyronine (T3), an FDA‑approved hormone used to treat hypothyroidism, to standard chemotherapy could help prevent tumors from growing back after treatment. The findings were published in the journal Molecular Therapy Oncology .
"Most chemotherapy drugs work by killing rapidly dividing cells – including cancer cells, but also many healthy ones. This is why chemotherapy can be so toxic," said Zeng‑jie Yang, MD, PhD, a Professor and member of the Cancer Epigenetics Institute at Fox Chase.
Medulloblastoma is typically treated with surgery, chemotherapy, and radiation, which can be lifesaving but are highly aggressive and often fail to prevent reoccurrence. Up to 30% of patients experience tumor regrowth. The research team, led by Yang, takes a different approach.
Encouraging Tumor Cells to Grow Up
The study focuses on differentiation therapy, which encourages tumor cells to mature into a normal‑like state in which they stop dividing.
"Differentiation is essentially cell maturation," Yang said. "Instead of killing tumor cells directly, we push them to grow into mature cells that no longer multiply."
The researchers used T3, the active form of thyroid hormone, to trigger this maturation process. Differentiated tumor cells are far less likely to drive tumor growth or relapse.
A Powerful Combination
Because chemotherapy and differentiation therapy stop tumor growth in different ways, the researchers tested whether combining them would be more effective.
In laboratory and animal models, chemotherapy followed by T3:
- suppressed tumor growth more effectively than chemotherapy alone;
- allowed lower doses of chemotherapy to achieve similar results;
- prevented tumors from regrowing after treatment ended; and
- worked against tumor cells resistant to chemotherapy.
In mouse models, tumors treated with chemotherapy alone eventually returned. When chemotherapy was followed by T3, tumor regrowth was markedly suppressed and survival was significantly extended.
Because medulloblastoma primarily affects children, safety was a major focus of the study. Although T3 has been prescribed for decades, high doses can temporarily increase heart rate.
The researchers found that T3 caused only a brief, mild increase in heart rate, that was easily controlled with propranolol, a commonly prescribed beta‑blocker. Importantly, propranolol did not reduce T3's anti‑tumor effects or add toxicity.
"This showed us that potential side effects are manageable using existing medications," said Yang.
Moving Toward Clinical Trials
Because T3 is already FDA‑approved, inexpensive, and well‑studied, this strategy could move to patients faster than many experimental cancer drugs.
A multicenter pediatric clinical trial is now underway with support from the Pediatric Neuro‑Oncology Consortium, a national network of children's hospitals. The trial will evaluate whether adding T3 to standard treatment can safely improve outcomes for children with medulloblastoma.
"Chemotherapy reduces tumor size by killing cells," Yang said. "T3 helps prevent the remaining cells from coming back. Together, they may offer children a better chance at long‑term survival with fewer side effects."
Read the full study here: https://www.sciencedirect.com/science/article/pii/S2950329926001116
