Is the hypoxia-inducible factor pathway important in gastric cancer?
AffiliationDepartment of Gastrointestinal Surgery, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital, South Moor Road, Wythenshawe, M23 9LT, UK.
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AbstractTumour 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.
CitationIs the hypoxia-inducible factor pathway important in gastric cancer? 2005, 41 (18):2792-805 Eur. J. Cancer
JournalEuropean Journal of Cancer
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