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Curr Pharm Des. 2009;15(33):3839-43.

HIF-1 inhibitors for cancer therapy: from gene expression to drug discovery.

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  • 1The Johns Hopkins University Schoolof Medicine, Baltimore, MD 21205, USA. gsemenza@jhmi.edu

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1alpha and HIF-1alpha subunits, which is activated in response to reduced O2 availability. HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. Increased HIF-1alpha levels, as determined by immunohistochemical analysis of tumor biopsy specimens, is associated with increased mortality in many human cancers. Drugs that inhibit HIF-1 activity and have anti-cancer effects in vivo have been identified and clinical trials are warranted to establish the contexts in which addition of such agents to therapy protocols will result in increased patient survival.

PMID:
19671047
[PubMed - indexed for MEDLINE]
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