Development of a non-radioactive assay for screening compounds for redifferentiating human thyroid cancer cells

• Grant number: 24/20484-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ileana Gabriela Sánchez de Rubió
• Grantee: Camila da Silva Neves
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Most cases of differentiated thyroid cancer (DTC) have a favorable prognosis; however, approximately 10% progress with metastasis and may not respond to conventional radioiodine therapy (RAI). Poorly differentiated cancer and anaplastic thyroid carcinoma (ATC) are the rarest types (1-2%) and the most aggressive, highly undifferentiated, radioiodine-refractory, resistant to chemotherapy or acquire treatment resistance, the survival rate ranges from 3 to 25 months post-diagnosis. Iodine uptake by thyroid cells depends on the expression and proper localization of the Na+/I- symporter (NIS). In more aggressive DTC and ATC NIS expression is silenced which is the primary cause of RAI treatment failure. For these cases, research has focused on adjuvant compounds that re-differentiate the tumor cell and increase iodine uptake to enable the reuse of radioiodine therapy. Therefore, identifying new compounds with this activity may be highly relevant. Current methods to evaluate iodine uptake in vivo and in vitro utilize radioactive material. Preliminary experiments to establish a non-radioactive assay for human cells have been initiated but showed limited sensitivity. Thus, the objectives of this project are to standardize a non-radioactive assay to assess iodine uptake in human thyroid cell lines and to identify compounds capable of re-differentiating thyroid cells. Various assay conditions and compounds available in the laboratory will be tested in ATC cells. If any compounds increase iodine uptake, the expression of NIS and other thyroid-specific genes will be analyzed by real-time PCR. By the end of the project, we aim to establish a non-radioactive assay to assess the re-differentiation of human tumor cells and identify compounds that enhance iodine uptake, which could be of significant clinical interest.