Abstract
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α 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-1α 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.
Keywords: Angiogenesis, cancer, chemotherapy, hypoxia-inducible factor, invasion, metastasis, metronomic therapy, oxygen
Current Pharmaceutical Design
Title: HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery
Volume: 15 Issue: 33
Author(s): G. L. Semenza
Affiliation:
Keywords: Angiogenesis, cancer, chemotherapy, hypoxia-inducible factor, invasion, metastasis, metronomic therapy, oxygen
Abstract: Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α 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-1α 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.
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Cite this article as:
Semenza L. G., HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery, Current Pharmaceutical Design 2009; 15 (33) . https://dx.doi.org/10.2174/138161209789649402
DOI https://dx.doi.org/10.2174/138161209789649402 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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