Aurora kinase A inhibitors: promising agents in antitumoral therapy

Expert Opin Ther Targets. 2014 Dec;18(12):1377-93. doi: 10.1517/14728222.2014.956085. Epub 2014 Sep 9.

Abstract

Introduction: Aurora proteins are serine/threonine kinases with critical functions during mitosis. Aurora A, one of the members of this family, participates in crucial processes including mitotic entry, DNA damage checkpoint recovery and centrosome and spindle maturation. Aurora A is frequently overexpressed in human cancers and, when inhibited, impairs cell proliferation.

Areas covered: Here, we review the preclinical studies that support the use of Aurora A inhibitors in antitumoral strategies. We also discuss past or current clinical trials using Aurora A inhibitors in multiple tumor types. We pay special attention to Alisertib, a potent and selective Aurora A inhibitor currently in Phase III.

Expert opinion: The potential of Aurora A inhibitors in the treatment of cancer depends on many factors, mainly related with the molecular status of tumor cells. Yet, we still need to find proper biomarkers to select those patients that better react to Aurora A inhibitors. Furthermore, their effect could significantly improve when used in combination with other drugs. Although some clinical trials are already testing the cooperative effect of different antitumoral drugs, additional preclinical studies are necessary to establish the best combinations. Here, we discuss some possibilities that could be explored in future studies.

Keywords: Alisertib; Aurora A; MLN8237; cancer; clinical trials; kinase inhibitors; mitosis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Aurora Kinase A / antagonists & inhibitors*
  • Aurora Kinase A / metabolism
  • Clinical Trials as Topic / methods
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Aurora Kinase A