A recent study suggests that thyroid hormones could significantly improve the effectiveness of treatments for medulloblastomas, the most commonly diagnosed malignant brain tumors in children.
Medulloblastoma, a brain tumor that develops in the cerebellum, mainly affects young children, often before the age of 10.
Despite very aggressive therapy, including surgery followed by radiation and cytotoxic chemotherapy, overall survival rates are around 60% and have remained at this level for almost 40 years.
Additionally, the toxicity of these treatments to the developing brain, particularly radiation therapy, means that medulloblastoma survivors often suffer lifelong complications, including intellectual disability, growth retardation, increased risk of secondary malignancies, and hearing loss.
Unfortunately, radiotherapy remains essential for the treatment of this cancer, making it very difficult to avoid these side effects. Identifying more effective and less toxic therapies is therefore absolutely necessary to improve both the survival and quality of life of children with this disease.
Abnormal development
Currently available data indicate that the cancer cells responsible for medulloblastomas appear in the early stages of embryonic development: instead of differentiating correctly into mature neurons, the evolution of the cells of the forming cerebellum is disrupted and instead leads to the appearance of abnormal cells, which acquire many cancerous characteristics making them extremely difficult to eliminate.
The researchers’ hard work, however, has highlighted a potential chink in the medulloblastoma armor: unlike other cancer cells that completely lose their initial functional cellular identity (through a process called dedifferentiation) and become atypical and uncontrollable, those of medulloblastomas retain their property of differentiating into completely normal neurons. In other words, instead of trying at all costs to eliminate medulloblastomas using toxic treatments, it would be possible to slow the growth of these tumors by forcing the cancer cells to evolve into a stage of mature neurons.
T3 hormone to the rescue
It has long been known that thyroid hormones are essential for brain development, particularly the cerebellum, and that low blood levels of these hormones (hypothyroidism) are frequently observed in patients with medulloblastoma.
In a very important study, it is suggested that the thyroid hormone 3,5,3′–triiodo-L-thyronine (T3) could also play a very important role in the treatment of medulloblastoma by accelerating the transformation of cancer cells into normal cells (1). The researchers were able to show that T3 causes the activation of a protein (NeuroD1) that triggers a cascade of events leading to the transformation of cancer cells into neurons. Better still, this effect seems to translate into a significant reduction in tumor burden: when models grafted with medulloblastoma cells taken from young patients were treated with T3, the tumors shrank dramatically, with a parallel significant increase in the survival of the animals.
The low cost of T3, its very favorable safety profile, and its near universal availability make it a very attractive treatment strategy for medulloblastomas. It is hoped that this major scientific discovery will translate into clinical trials as soon as possible to determine its impact on this devastating cancer.
(1) Yang Y et coll. «Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells». Cancer Cell 2024; 42: 1434-1449.e5.
