Hypoxia-inducible factor 1 and cancer pathogenesis.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates adaptive responses to hypoxia. HIF-1 activity is increased in the majority of human cancers as a result of genetic alterations and intratumoral hypoxia. HIF-1 activates the transcription of genes that increase O(2) availability by stimulating angiogenesis or that reprogram cellular metabolism to adapt to reduced O(2) availability. Proof of principle studies in mouse models suggests that inhibition of HIF-1 activity may have therapeutic effects, especially in combination with other anticancer drugs.