Exploring Advanced Brain Tumor Models in High-Grade Glioma Research: Evaluating Euphol Response and Tumor Microenvironment Contributions to Treatment Resistance

• Grant number: 24/13194-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 15, 2024
• End date: December 14, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Rui Manuel Vieira Reis
• Grantee: Mirella Baroni Milan
• Supervisor: Anna Golebiewska
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Institution abroad: Luxembourg Institute Of Health, Luxembourg
• Associated to the scholarship: 21/07957-5 - Antitumor activity evaluation of euphol compound in the treatment of GBM through a preclinical trial with xenografts derived from patients, BP.PD

Abstract

High-grade gliomas (HGGs) are aggressive brain tumors characterized by rapid progression and resistance to conventional therapies, resulting in poor patient prognoses. To overcome these challenges, more sophisticated and representative preclinical models are required. This project has two main aims: first, to learn and develop advanced HGG preclinical models such as immunocompetent organoids, patient-derived orthotopic xenografts (PDOX), and humanized models. The second objective is to investigate the therapeutic potential of euphol, a natural compound with anti-cancer properties, in these HGG models. Methodologies include developing and characterizing organoids and PDOX from patient samples to mimic the tumor microenvironment (TME) more accurately and creating humanized models with human immune cells in mice to study interactions between glioma and the immune system. Comprehensive analyses of tumor responses to euphol treatment will be conducted, evaluating changes in HGG growth and TME. Implementing and utilizing these methodologies not only propel the understanding of HGG biology but also offer the potential to improve precision in creating new personalized therapeutic strategies, driving substantial progress in precision oncology. Moreover, this study will also elucidate the mechanisms underlying euphol's anti-tumor effects.