Antioxidant defense mechanisms in adrenococortical tumorigenesis

• Grant number: 23/14199-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Margaret de Castro
• Grantee: Aline Faccioli Bodoni
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Context: The molecular bases of adrenocortical tumors (ACT) are only partially established. Changes in antioxidant defense mechanisms have been associated with increased risk of several types of cancer. Dysregulation of this system may also be associated with tumor growth, metastasis, and drug resistance. However, little data shows how oxidative stress-related biomarkers are involved in the pathophysiology of adrenal cancer.Aim: Identify genes of the antioxidant defense system involved in the tumorigenesis of adult and pediatric adrenocortical tumors. To evaluate the effects of the deregulation of oxidative stress-related genes on processes related to tumorigenesis and metastasis in adrenocortical tumor cell lines. Additionally, to investigate the effect of antitumor compounds on the antioxidant defense system and its relationship with the resistance of these adrenal cells to treatments.Methods: Using in silico analysis, we will identify the expression of genes involved in the maintenance of mechanisms of antioxidant defense and its association with disease outcome in adrenocortical in ACT. In the immortalized tumor adrenal cells (H295R) will assess how overexpressing/inhibiting those genes could affect biological processes involved in tumorigenesis, mitochondrial activity, metastasis, drug resistance, and the response to treatment.Perspectives: The results from this project are expected to contribute to research on new therapeutic targets and to open perspectives for the treatment of metastatic or recurrent ACC patients.