HIF-1 and tumor progression: pathophysiology and therapeutics

✍ Scribed by Gregg L. Semenza

• Book ID: 118626456
• Publisher: Elsevier Science
• Year: 2002
• Tongue: English
• Weight: 316 KB
• Volume: 8
• Category: Article
• ISSN: 1471-4914
• DOI: 10.1016/s1471-4914(02)02317-1

✦ Synopsis

Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1β subunit and an oxygen-and growth-factor-regulated HIF-1α subunit. In xenografts, tumor growth and angiogenesis are correlated with HIF-1 expression. In human cancers, HIF-1α is overexpressed as a result of intratumoral hypoxia and genetic alterations affecting key oncogenes and tumor suppressor genes. HIF-1α overexpression in biopsies of brain, breast, cervical, esophageal, oropharyngeal and ovarian cancers is correlated with treatment failure and mortality. Increased HIF-1 activity promotes tumor progression, and inhibition of HIF-1 could represent a novel approach to cancer therapy.