Screening of compounds that cross the blood-brain barrier to identify new therapies in pediatric ependymomas

• Grant number: 23/08300-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2023
• Effective date (End): April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Eduardo Afonso da Silva Pereira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Ependymomas (EPNs) are rare neoplasms that develop from the ependymal cells that line the ventricular system of the brain and the spinal canal. It is the third most common tumor of the central nervous system (CNS) in children and can develop in the supratentorial region (ST), posterior fossa (FP) and spinal cord (SP). Intracranial ependymomas are the most frequent in childhood and are currently classified into the main molecular subgroups: ST-ST-ZFTA and ST-YAP1 region (supratentorial) and in the posterior fossa PF-A and PF-B Conventionally, surgical resection and radiotherapy is the main effective treatment for EPNs, with chemotherapy being a therapy with no clinical benefits for patients with EPNs; mainly due to the heterogeneous and complex characteristics of these tumors, as well as the inaccessibility of the tumors. CNS tumors face several obstacles to chemotherapy treatment due to the presence of the blood-brain barrier (BBB), one of the factors responsible for the therapeutic failure of ependymomas. Currently, there is little knowledge of drugs that can cross the BBB to effectively treat these tumors. Thus, the main objective of this work is to carry out a screening of non-classical drugs that are known to cross the BBB, acting effectively in EPNs. Drug screening will be performed using the High Content Screening (HCS) methodology using 2D and 3D tumor models. The effect of the best drugs on reducing cell viability, cell migration and invasion will be evaluated, as well as the modulation of target proteins after drug treatment.