Investigation of the cellular and molecular effects of reversine in glioma models

• Grant number: 19/26058-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2020
• End date: December 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: João Agostinho Machado Neto
• Grantee: Camila Yumi Soares Hirakata
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Gliomas belong to a heterogeneous group of brain tumors with distinct biological and clinical properties that include molecular complexity, as well as inconsistencies in histopathological classification, resulting in an inaccurate prediction of disease progression and failure to use standard therapy. A challenge for the treatment of gliomas is the high recurrence rates. Despite the great advances in the understanding of biology and molecular changes in gliomas, very little has been translated into new therapies. Auroras are serine/threonine kinases required for multiple aspects in mitotic regulation in eukaryotic cells. In gliomas, AURKA expression is higher in later stages of the disease, is associated with proliferation markers and angiogenesis, and predicts worse prognosis. Similarly, AURKB expression is higher in glioblastomas, is related to chemoresistance to temozolomide, and negatively impacts clinical outcome. Reversine is an ATP analog and has been reported as a potent selective multikinase inhibitor for AURKA, AURKB, MSP1, and JNK and has potential antineoplastic activity. Given the importance of aurora kinases for gliomas, this research project aims to investigate the cellular and molecular effects of reversine treatment in human glioma models. Our expectation is to consolidate the findings that aurora kinases may be potential targets and propose a new drug to compose the chemotherapeutic arsenal in the treatment of gliomas.