In 2023, researchers from Fox Chase Cancer Center found thyroid hormone triiodothyronine (T3), commonly used to treat hypothyroidism, can induce differentiation in medulloblastoma cells, the most common malignant brain tumor in children.
Medulloblastoma typically develops in the cerebellum, the part of the brain responsible for balance, coordination, and fine motor control. It usually affects children under the age of 10 and can grow and spread quickly through the cerebrospinal fluid. Conventional treatment usually includes surgery, radiation, and chemotherapy—an aggressive combination that can damage the developing brain and lead to long-term side effects like learning difficulties, hormonal problems, and hearing loss.
In light of these risks, researchers are exploring gentler, more targeted therapies. T3 treatment is one such option. Researchers found that T3 can encourage tumor cells to mature into normal, specialized cells, effectively stopping tumor growth.
How does T3 induce differentiation?
T3 is the active thyroid hormone, which is converted. from T4 (thyroxine), produced by the thyroid gland. T3 promotes a process called terminal differentiation, where an immature cell finishes developing into its final, specialized form. Instead of chaotically growing, the cell receives a signal from T3 to mature and specialize—essentially guiding it back onto its proper developmental path.
- T3 enters the cell and binds to special receptors (like keys fitting into locks).
- These receptors send a signal to the cell’s DNA to turn on specific “maturation” genes.
- One important gene T3 turns on is NeuroD1, which helps brain cells finish developing.
- T3 also blocks proteins that normally keep the cell immature, like EZH2.
- As a result, the cell stops acting like a cancer cell and starts behaving like a normal, healthy brain cell.
Interestingly, hypothyroidism is common in patients with medulloblastoma.
And children born to mothers with hypothyroidism have been shown to have a 41% higher risk of developing any form of childhood cancer compared to those whose mothers had normal thyroid function.
Thyroid hormones are essential for healthy development, especially during pregnancy. Maternal thyroid hormones, T3 and T4, guide brain development, immune programming, and the maturation of cells throughout the body. During pregnancy, a woman’s thyroid hormone production needs to increase by up to 50% to meet the demands of the growing fetus. If this increase doesn’t happen and thyroid hormone levels remain too low, especially during critical windows, the normal signals that tell fetal cells to grow up and specialize can be delayed or disrupted.
It’s possible that not all childhood cancers are purely genetic. Some may arise from missed or weakened developmental cues, especially those involving thyroid hormones in utero. If immature cells fail to receive proper signals to differentiate, they may remain in a stem-like, proliferative state, more vulnerable to turning cancerous later.
Supplementing with T3 in medulloblastoma may help correct a missed developmental cue, pushing immature cancer cells to differentiate into normal, functioning cells. This offers a new angle on treatment: not just killing cancer, but helping it to mature into healthy tissue.
Given that T3 is already FDA-approved, commonly used, and well-understood in both adults and children, it presents a promising opportunity for treatment.
T3 could offer a less toxic and more precise alternative to traditional cancer therapies, especially for vulnerable pediatric patients.
