Development of Zebrafish (Danio rerio) model of Multiple Endocrine Neoplasia type 2 (MEN2) to study the tumor mechanism of Medullary Thyroid Cancer (MTC) and evaluate the effect of new drugs in the treatment of MTC

• Grant number: 23/02964-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2023
• End date: October 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rui Monteiro de Barros Maciel
• Grantee: Janaina Aparecida de Lima Marques Siqueira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/02752-6 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management, AP.TEM

Abstract

The main objective of this project is to develop a novel model of Medullary Thyroid Cancer (MTC) using zebrafish to better understand the mechanisms related to carcinogenesis and progression. The transgenic fishes generated by Gateway strategy (Gal4-calca x UAS- RET) will be genotyped, and the tumor will be followed ten days post-fertilization regarding size, neovascularization, and presence of metastasis. This new model makes possible the study of MTC pathogenesis and the search for new therapeutic targets. The first drug to be tested will be vandetanib. Following it, we intend to test other target-therapy drugs, such as cabozantinib, for example and collaborate with researchers who have screening platforms for other compounds, such as chemotherapeutics, as an alternative to finding new non-target-directed agents. (AU)