The therapeutic potential of Aurora kinases targeting in glioblastoma: from preclinical research to translational oncology

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 98; no. 4; pp. 495 - 512
• Main Authors: de Almeida Magalhães, Taciani, de Sousa, Graziella Ribeiro, Alencastro Veiga Cruzeiro, Gustavo, Tone, Luiz Gonzaga, Valera, Elvis Terci, Borges, Kleiton Silva
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2020; Springer Nature B.V
• Subjects: Apoptosis; Aurora kinase; Biomedical and Life Sciences; Biomedicine; Brain cancer; Brain tumors; Cell division; Chemoresistance; Chemotherapy; Clinical trials; Drug development; Glioblastoma; Human Genetics; Internal Medicine; Molecular Medicine; Oncology; Radiation therapy; Review; Serine; Temozolomide; Therapeutic applications; Threonine; Clinical trial; Aurora kinases; Aurora kinases inhibitors; Glioblastoma
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-020-01895-x

Glioblastoma is the most common aggressive primary brain tumor. Standard care includes maximal safe surgical resection, radiation, and chemotherapy with temozolomide. However, the impact of this therapeutic approach on patient survival is disappointing and poor outcomes are frequently observed. Therefore, new therapeutic targets are needed to treat this potentially deadly tumor. Aurora kinases are one of today’s most sought-after classes of therapeutic targets to glioblastoma therapy. They are a family of proteins composed of three members: Aurora-A, Aurora-B, and Aurora-C that play different roles in the cell division through regulation of chromosome segregation. Deregulation of these genes has been reported in glioblastoma and a progressive number of studies have shown that inhibition of these proteins could be a promising strategy for the treatment of this tumor. This review discusses the preclinical and early clinical findings on the potential use of the Aurora kinases as new targets for the treatment of glioblastoma.
Key messages
GBM is a very aggressive tumor with limited therapeutic options.
Aurora kinases are a family of serine/threonine kinases implicated in GBM pathology.
Aurora kinases are critical for glioblastoma cell growth, apoptosis, and chemoresistance.
Inhibition of Aurora kinases has a synergistic or sensitizing effect with chemotherapy drugs, radiotherapy, or with other targeted molecules in GBM.
Several Aurora kinase inhibitors are currently in clinical trials.