Targeting the hypoxia-inducible factor (HIF) pathway in cancer
- PMID: 19709449
- DOI: 10.1017/S1462399409001173
Targeting the hypoxia-inducible factor (HIF) pathway in cancer
Abstract
The central component of hypoxia sensing in the cell is the hypoxia-inducible factor (HIF) transcriptional complex. HIF activity is deregulated in many human cancers, especially those that are highly hypoxic. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Overexpression of HIF-alpha, the regulatory subunit of HIF, is associated with increased vascular density, severity of tumour grade, treatment failure and a poor prognostic outcome with conventional therapies. Therefore HIF is an attractive, although challenging, therapeutic target, and several different strategies have been developed to target HIF directly or indirectly in recent years. This review outlines the preclinical and clinical advances in this arena and discusses which cancers may benefit from HIF-targeted therapy.
Similar articles
-
Role of hypoxia-inducible factor-1alpha as a cancer therapy target.Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S61-75. doi: 10.1677/erc.1.01290. Endocr Relat Cancer. 2006. PMID: 17259560 Review.
-
Cellular redox status regulates hypoxia inducible factor-1 activity. Role in tumour development.J Exp Clin Cancer Res. 2007 Mar;26(1):39-50. J Exp Clin Cancer Res. 2007. PMID: 17550131 Review.
-
Targeting hypoxia cell signaling for cancer therapy.Cancer Metastasis Rev. 2007 Jun;26(2):341-52. doi: 10.1007/s10555-007-9059-x. Cancer Metastasis Rev. 2007. PMID: 17415529 Review.
-
Inhibiting hypoxia-inducible factor 1 for cancer therapy.Mol Cancer Res. 2006 Sep;4(9):601-5. doi: 10.1158/1541-7786.MCR-06-0235. Epub 2006 Aug 28. Mol Cancer Res. 2006. PMID: 16940159 Review.
-
Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level.J Cell Sci. 2006 Aug 15;119(Pt 16):3351-62. doi: 10.1242/jcs.03069. Epub 2006 Aug 1. J Cell Sci. 2006. PMID: 16882692
Cited by
-
Understanding the hypoxic niche of multiple myeloma: therapeutic implications and contributions of mouse models.Dis Model Mech. 2012 Nov;5(6):763-71. doi: 10.1242/dmm.008961. Dis Model Mech. 2012. PMID: 23115205 Free PMC article. Review.
-
Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence.BMC Biol. 2013 Aug 9;11:91. doi: 10.1186/1741-7007-11-91. BMC Biol. 2013. PMID: 23937926 Free PMC article.
-
A potentially common peptide target in secreted heat shock protein-90α for hypoxia-inducible factor-1α-positive tumors.Mol Biol Cell. 2012 Feb;23(4):602-13. doi: 10.1091/mbc.E11-06-0575. Epub 2011 Dec 21. Mol Biol Cell. 2012. PMID: 22190738 Free PMC article.
-
Cancer stem cells: a new framework for the design of tumor therapies.J Mol Med (Berl). 2011 Feb;89(2):95-107. doi: 10.1007/s00109-010-0685-3. Epub 2010 Oct 2. J Mol Med (Berl). 2011. PMID: 20890588 Review.
-
Clinicopathologic significance of HIF-1α, CXCR4, and VEGF expression in colon cancer.Clin Dev Immunol. 2010;2010:537531. doi: 10.1155/2010/537531. Epub 2010 Oct 7. Clin Dev Immunol. 2010. PMID: 20953377 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources