The repurposing of neuroactive drugs for high-grade gliomas: a preclinical approach in oncological neuroscience

• Grant number: 24/23717-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Marcos Vinicius Calfat Maldaun
• Grantee: Danielle Varin de Assis
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

High-grade gliomas (HGG), grades 3 and 4, are highly lethal tumors affecting both adults and children, including glioblastoma (GBM), diffuse astrocytomas, and diffuse midline gliomas (DMG). Despite the aggressive nature of current treatments for HGG, which combine surgery, radiotherapy, and/or chemotherapy, patients invariably experience tumor recurrence and progress to death. This underscores the urgent need to better understand the biology of these tumors to develop new therapeutic strategies. Neoplastic cells can recruit, modulate, and interact with local non-tumoral cells, including neurons, endothelial cells, glial cells, and immune cells within the central nervous system, forming a highly complex and dynamic tumor microenvironment (TME). This TME plays a crucial role in tumor progression and treatment resistance. In this context, oncological neuroscience has emerged as a field dedicated to investigating the interactions and connections within this tumor scenario, focusing on the communication between these cells. It contributes to the growing investigation of the TME in terms of tumor progression, genetic and epigenetic alterations. Tumorglia-neuron communication involves various mediators that create a self-sustaining environment, where neuronal activity and synaptic remodeling contribute to tumor progression and vice versa. Therapeutic approaches employing novel drugs have advanced in the field of neuro-oncology, such as repurposed neuroactive drugs or multi-drug compounds, showing great promise. This project aims to analyze the effects of pharmacological therapies using repurposed neuroactive drugs on tumor-glia-neuron communication and interaction, focusing on their mediators and cellular profiles in a murine model of high-grade glioma. Therefore, advancing knowledge in oncological neuroscience, particularly in cellular communication, will significantly enhance our understanding of the tumor scenario. This will pave the way for multi-target therapies, ultimately improving progression-free survival for patients affected by HGG. (AU)