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J Mol Med (Berl) ; 98(4): 495-512, 2020 04.
Article in English | MEDLINE | ID: mdl-32219470

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.


Subject(s)
Antineoplastic Agents/pharmacology , Aurora Kinases/antagonists & inhibitors , Glioblastoma/metabolism , Protein Kinase Inhibitors/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Aurora Kinases/genetics , Aurora Kinases/metabolism , Biomarkers, Tumor , Glioblastoma/drug therapy , Glioblastoma/etiology , Glioblastoma/pathology , Humans , Molecular Targeted Therapy , Multigene Family , Protein Kinase Inhibitors/therapeutic use , Translational Research, Biomedical , Xenograft Model Antitumor Assays
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