期刊
CURRENT PHARMACEUTICAL DESIGN
卷 15, 期 33, 页码 3839-3843出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161209789649402
关键词
Angiogenesis; cancer; chemotherapy; hypoxia-inducible factor; invasion; metastasis; metronomic therapy; oxygen
资金
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1 alpha and HIF-1 alpha subunits, which is activated in response to reduced O-2 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-1 alpha 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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