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 O₂ availability by stimulating angiogenesis or that reprogram cellular metabolism to adapt to reduced O₂ 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.