Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress

Semin Oncol. 2015 Dec;42(6):832-48. doi: 10.1053/j.seminoncol.2015.09.022. Epub 2015 Sep 24.

Abstract

The Aurora kinase family of kinases (Aurora A, B, and C) are involved in multiple mitotic events, and aberrant expression of these kinases is associated with tumorigenesis. Aurora A and Aurora B are validated anticancer targets, and the development of Aurora kinase inhibitors has progressed from preclinical to clinical studies. A variety of Aurora A, B and pan-Aurora kinase inhibitors have entered the clinic. The main side effects include febrile neutropenia, stomatitis, gastrointestinal toxicity, hypertension, and fatigue. Responses including complete remissions have been described in diverse, advanced malignancies, most notably ovarian cancer and acute myelogenous leukemia. This review highlights the biologic rationale for Aurora kinase as a target, and clinical trials involving Aurora kinase inhibitors, with particular emphasis on published early phase studies, and the observed anti-tumor activity of these agents.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase B / antagonists & inhibitors
  • Aurora Kinases / antagonists & inhibitors*
  • Benzamides / therapeutic use
  • Benzazepines / therapeutic use
  • Benzimidazoles / therapeutic use
  • Clinical Trials as Topic
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Norbornanes / therapeutic use
  • Organophosphates / therapeutic use
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • Quinazolines / therapeutic use
  • Urea / analogs & derivatives
  • Urea / therapeutic use

Substances

  • 1-cyclopropyl-3-(3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl)urea
  • 2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate
  • Antineoplastic Agents
  • Benzamides
  • Benzazepines
  • Benzimidazoles
  • ENMD 2076
  • Heterocyclic Compounds, 3-Ring
  • MLN8054
  • MSC1992371A
  • N-(2-(6-(4-cyclobutylamino-5-trifluoromethylpyrimidine-2-ylamino)-1,2,3,4-tetrahydro-1,4-epiazano-naphthalen-9-yl)-2-oxo-ethyl)acetamide
  • Norbornanes
  • Organophosphates
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Quinazolines
  • tozasertib
  • Urea
  • AURKA protein, human
  • AURKB protein, human
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinases
  • danusertib