HIF-1 and tumor progression: pathophysiology and therapeutics

Abstract

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-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlated with HIF-1 expression. In human cancers, HIF-1 alpha is overexpressed as a result of intratumoral hypoxia and genetic alterations affecting key oncogenes and tumor suppressor genes. HIF-1 alpha 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.