Evaluation of 5-azacitidine treatment in cisplatin-resistant germ cell tumor models

• Grant number: 24/06770-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Eleni Solange de Brito Gomes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated research grant: 19/07502-8 - Investigation of the transcription factors inducing Epithelial-Mesenchymal Transition (EMT) in germ cells tumors, AP.JP

Abstract

Germ cell tumors (GCTs) are benign and malignant neoplasms derived from primordial germ cells. The treatment for these tumors includes surgery and chemotherapy, with cisplatin being one of the most widely used chemotherapeutic agents. Cisplatin binds to DNA, altering its structure and preventing its duplication and transcription, leading to cell death through apoptosis. However, the resistance of some patients to this compound remains an ongoing challenge. Therefore, overcoming cisplatin resistance through the use of other chemotherapeutic agents could enhance the survival rates of these patients. Recently, 5-azacitidine received approval from the Food and Drug Administration (FDA) for the treatment of pediatric patients with leukemia. There is speculation that this drug may also be effective in treating other tumors, including GCTs. Thus, the aim of this proposal is to evaluate the effect of 5-azacitidine treatment in a cisplatin-resistant GCT animal model. To this end, eight-week-old athymic nude mice (NU/J), provided by the Bioterium-CPOM-HCB, will be used. GCT cell lines (NTERA-2 and JEG-3, both parental and cisplatin-resistant) will be implanted subcutaneously, and once the tumors develop, treatments with 5-azacitidine and cisplatin will begin. Tumor progression will be monitored, and histological analysis, DNA methylation analysis in tumors, and gene expression analysis will be conducted. Establishing the in vivo model of cisplatin-resistant GCTs and treatment with 5-azacitidine will contribute to the development of new therapeutic approaches.