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Obstetrics and Gynecology International
Volume 2010, Article ID 580971, 8 pages
http://dx.doi.org/10.1155/2010/580971
Review Article

Hypoxia-Inducible Factor-1 as a Therapeutic Target in Endometrial Cancer Management

1Department of Gynaecological Oncology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands
2Department of Pathology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

Received 31 October 2009; Accepted 22 December 2009

Academic Editor: Paul J. Hoskins

Copyright © 2010 Laura M. S. Seeber et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In the Western world, endometrial cancer (EC) is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1 𝛼 (HIF-1 𝛼 ) plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1 𝛼 protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials.