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Drug Discov Today. 2007 Oct;12(19-20):853-9. Epub 2007 Sep 18.

Evaluation of HIF-1 inhibitors as anticancer agents.

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  • 1Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway, Suite 671, Baltimore, MD 21205, USA. gsemenza@jhmi.edu

Abstract

Hypoxia-inducible factor 1 (HIF-1) regulates the transcription of many genes involved in key aspects of cancer biology, including immortalization, maintenance of stem cell pools, cellular dedifferentiation, genetic instability, vascularization, metabolic reprogramming, autocrine growth factor signaling, invasion/metastasis, and treatment failure. In animal models, HIF-1 overexpression is associated with increased tumor growth, vascularization, and metastasis, whereas HIF-1 loss-of-function has the opposite effect, thus validating HIF-1 as a target. In further support of this conclusion, immunohistochemical detection of HIF-1alpha overexpression in biopsy sections is a prognostic factor in many cancers. A growing number of novel anticancer agents have been shown to inhibit HIF-1 through a variety of molecular mechanisms. Determining which combination of drugs to administer to any given patient remains a major obstacle to improving cancer treatment outcomes.

PMID:
17933687
[PubMed - indexed for MEDLINE]
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