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

J Mol Med (Berl). 2020 Apr;98(4):495-512. doi: 10.1007/s00109-020-01895-x. Epub 2020 Mar 26.

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.

Keywords: Aurora kinases; Aurora kinases inhibitors; Clinical trial; Glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Aurora Kinases