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

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Abstract

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.

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Funding

This work was supported by São Paulo Research Foundation (FAPESP), Grant Nos. 2009/50118-2, 2016/19820-6, 2017/06511-8, and 2018/23372-4, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Grant Nos. 151760/2018-7 and 409711/2018-7.

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  1. Taciani de Almeida Magalhães and Graziella Ribeiro de Sousa contributed equally to this work.

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  1. Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, 14048-900, São Paulo, Brazil

    Taciani de Almeida Magalhães, Graziella Ribeiro de Sousa & Luiz Gonzaga Tone

  2. Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14048-900, São Paulo, Brazil

    Gustavo Alencastro Veiga Cruzeiro, Luiz Gonzaga Tone, Elvis Terci Valera & Kleiton Silva Borges

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  1. Taciani de Almeida Magalhães
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de Almeida Magalhães, T., de Sousa, G.R., Alencastro Veiga Cruzeiro, G. et al. The therapeutic potential of Aurora kinases targeting in glioblastoma: from preclinical research to translational oncology. J Mol Med 98, 495–512 (2020). https://doi.org/10.1007/s00109-020-01895-x

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