Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Academic Article uri icon

Overview

abstract

  • PURPOSE: The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle. We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457. EXPERIMENTAL DESIGN: We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models. RESULTS: In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed >10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1 as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values<0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P

publication date

  • September 1, 2008

Research

keywords

  • Enzyme Inhibitors
  • Ovarian Neoplasms
  • Piperazines
  • Protein Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC2766914

Scopus Document Identifier

  • 53049109358

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-07-4922

PubMed ID

  • 18765535

Additional Document Info

volume

  • 14

issue

  • 17