Abstract
Solid tumors with areas of hypoxia are the most aggressive and difficult tumors to treat and are a major reason for treatment failure. Previous attempts to treat hypoxic tumors have been largely unsuccessful and new agents are needed. The cellular response to hypoxia is controlled by the hypoxia inducible factor-1 (HIF-1) transcription factor. HIF-1 consists of an oxygen regulated alpha subunit and a constitutively expressed beta subunit, which bind and translocate to the nucleus to activate transcription of a range of genes involved in increasing glycolysis, inhibition of apoptosis and promotion of angiogenesis and metastasis. The activity of the HIF-1 complex is primarily controlled by levels of the alpha subunit and a series of mechanisms exist to control activation of the HIF-1 pathway. HIF-1α is over-expressed in a large number of human tumors and its over-expression correlates with poor prognosis and treatment failure. HIF-1 is therefore an important target for cancer chemotherapy. This review summarizes the literature surrounding the control of HIF-1, its role in cancer and potential drugs to target the pathway for cancer therapy.
Keywords: hypoxia inducible factor, cancer drug target, solid tumors, transcription factor, angiogenesis, metastasis, cancer therapy
Current Cancer Drug Targets
Title: Hypoxia Inducible Factor as a Cancer Drug Target
Volume: 3 Issue: 6
Author(s): Sarah J. Welsh and Garth Powis
Affiliation:
Keywords: hypoxia inducible factor, cancer drug target, solid tumors, transcription factor, angiogenesis, metastasis, cancer therapy
Abstract: Solid tumors with areas of hypoxia are the most aggressive and difficult tumors to treat and are a major reason for treatment failure. Previous attempts to treat hypoxic tumors have been largely unsuccessful and new agents are needed. The cellular response to hypoxia is controlled by the hypoxia inducible factor-1 (HIF-1) transcription factor. HIF-1 consists of an oxygen regulated alpha subunit and a constitutively expressed beta subunit, which bind and translocate to the nucleus to activate transcription of a range of genes involved in increasing glycolysis, inhibition of apoptosis and promotion of angiogenesis and metastasis. The activity of the HIF-1 complex is primarily controlled by levels of the alpha subunit and a series of mechanisms exist to control activation of the HIF-1 pathway. HIF-1α is over-expressed in a large number of human tumors and its over-expression correlates with poor prognosis and treatment failure. HIF-1 is therefore an important target for cancer chemotherapy. This review summarizes the literature surrounding the control of HIF-1, its role in cancer and potential drugs to target the pathway for cancer therapy.
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Cite this article as:
Welsh J. Sarah and Powis Garth, Hypoxia Inducible Factor as a Cancer Drug Target, Current Cancer Drug Targets 2003; 3 (6) . https://dx.doi.org/10.2174/1568009033481732
DOI https://dx.doi.org/10.2174/1568009033481732 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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