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Keywords:

  • angiogenesis;
  • cyclooxygenase;
  • drug reprofiling;
  • hypoxia-inducible factor-1;
  • intratumoral hypoxia;
  • prostaglandins;
  • sphingolipids

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that immortalizes tumors by inducing key genes in cancer biology, including angiogenesis, glycolysis, invasion, and metastasis. Overexpression of HIF-1α is thus associated with resistance to cancer chemotherapy and increased patient mortality in several cancer phenotypes. In the present review, we summarize the role of intratumoral hypoxia and bioactive lipids in enhancing HIF-1 activity, critically discussing the potential for HIF-1α inhibitors in cancer chemotherapy. Considering preclinical studies, HIF-1 inhibitors appear to have antitumor effects and thus represent a novel therapeutic strategy.