Assessment of Efficacy and Toxicity of T3 for Medulloblastoma Treatment

PROJECT SUMMARY/ABSTRACT Medulloblastoma (MB) is the most common malignant brain tumor in children. Despite conventional treatment including surgery, chemotherapy and radiation, a significant proportion of MB patients still succumbs to this disease. Moreover, almost all patients suffer long-term side effects of the aggressive treatment, such as hearing loss and cognitive deficit. Improved strategies to treat MB are urgently needed. Our recent studies have unveiled that T3, the active form of thyroid hormone, inhibits MB tumor growth by inducing terminal differentiation of tumor cells in mice, without causing noticeable weight loss. These findings suggest that T3, an FDA-approved drug for hypothyroidism, holds promise as a potential approach for MB treatment. To translate our discoveries into clinical trials, we propose to delve deeper into the toxicity and therapeutic efficacy of T3 in mice. Specifically, our research will focus on two specific aims: 1. Aim 1: Evaluate the toxicity, pharmacokinetic, and pharmacodynamic properties of T3 in tumor-bearing mice. 2. Aim 2: Examine the therapeutic efficacy of T3 in combination with cytotoxic drugs or irradiation. Our studies aim to furnish the preclinical data necessary for designing clinical trials to assess T3 as a potential treatment for MB in patients, paving the way to apply T3 as a novel therapeutic modality for MB.