The role of hypoxia inducible factor-1alpha in gynecological cancer

Laura M.S. Seeber, Nicole Horrée, Marc A.G.G. Vooijs, A. Peter M. Heintz, Elsken van der Wall, René H.M. Verheijen, Paul J. Van Diest

Research output: Contribution to journalReview article

Abstract

Understanding the mechanisms of carcinogenesis and progression of gynecological tumors is important as these insights might lead to improved diagnostic tools for the pathologist, improved prediction of prognosis, response to therapy, and eventually better biology-based disease management, thereby improving prognosis and quality of life for the individual patient. Hypoxia is an important event in carcinogenesis because it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases and poorer survival. Although selecting patients with hypoxic tumors may therefore be clinically important, there is no consensus as to the method best suited for routine assessment of hypoxia. One of the potential tumor hypoxia markers is hypoxia inducible factor 1 (HIF-1). HIF-1 is the key cellular survival protein under hypoxia, and is associated with tumor progression and metastasis in various solid tumors. In this review, we show that in gynecological cancers, HIF-1A is emerging as an important factor in carcinogenesis, and that overexpression of HIF-1A and its target genes CA9 and SLC2A1 seems associated with shorter progression free- and overall survival. Since hypoxia and HIF-1A expression are associated with treatment failure, targeting HIF-1A could be an attractive therapeutic strategy with the potential for disrupting multiple pathways crucial for tumor growth. Currently, HIF-1A inhibitors are being studied in clinical trials in recurrent ovarian- and cervical cancer, and trials in other gynecological cancers are expected.

Original languageEnglish (US)
Pages (from-to)173-184
Number of pages12
JournalCritical Reviews in Oncology/Hematology
Volume78
Issue number3
DOIs
StatePublished - Jun 1 2011

Keywords

  • Cervical cancer
  • Endometrial cancer
  • Hypoxia
  • Hypoxia inducible factor-1alpha
  • Ovarian cancer
  • Prognosis
  • Therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

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  • Cite this

    Seeber, L. M. S., Horrée, N., Vooijs, M. A. G. G., Heintz, A. P. M., van der Wall, E., Verheijen, R. H. M., & Van Diest, P. J. (2011). The role of hypoxia inducible factor-1alpha in gynecological cancer. Critical Reviews in Oncology/Hematology, 78(3), 173-184. https://doi.org/10.1016/j.critrevonc.2010.05.003