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Is the hypoxia-inducible factor pathway important in gastric cancer?
Griffiths, Ewen A Pritchard, S A Welch, I M Price, Patricia M West, Catharine M L
Griffiths, Ewen A
Pritchard, S A
Welch, I M
Price, Patricia M
West, Catharine M L
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Abstract
Tumour hypoxia is well recognised in oncology to be a key factor resulting in treatment resistance and poor prognosis. Hypoxia leads to the expression of a number of gene products that are involved in tumour progression, invasion and metastasis formation. The most important of these proteins is thought to be hypoxia-inducible factor-1alpha (HIF-1alpha), which appears to be a master regulator of the cellular response to hypoxia. HIF-1alpha expression is associated with a poor prognosis and treatment response in a number of tumour sites. There is some evidence that the HIF-1alpha pathway might be involved in gastric carcinogenesis. Studies have shown reactive oxygen species from Helicobacter pylori, associated with the development of gastric cancer, stabilise HIF-1alpha. Non-steroidal anti-inflammatory drugs, shown to reduce the risk of gastric cancer, can decrease HIF-1alpha expression. Although a large study correlating HIF-1alpha expression with prognosis is lacking in gastric cancer, the immunohistochemical expression of HIF-1alpha target genes (Glut-1, VEGF, CA9, iNOS) is associated with a poor prognosis. In addition, the targeted inhibition of HIF-1alpha has been shown to inhibit the growth of gastric tumours in animals. Increased understanding of the importance of hypoxia and the HIF-1alpha pathways may therefore hold the key to prevention strategies, improved selection of patients for adjuvant therapy and new treatments for the disease.
Description
Date
2005-12
Publisher
Collections
Keywords
Cancer Proteins
Stomach Cancer
Tumour Markers
Stomach Cancer
Tumour Markers
Type
Article
Citation
Is the hypoxia-inducible factor pathway important in gastric cancer? 2005, 41 (18):2792-805 Eur. J. Cancer