Hypoxia Inducible Factor-1α: A New Anticancer Drug Target

Hypoxia is an important characteristic of neoplasma and some other diseases. For this reason, it is becoming an attractive research area to inhibit tumor growth by utilizing the hypoxia environment. The discovery of hypoxia inducible factor-1 (HIF-1) has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past 15 years. Now it is generally accepted that HIF-1 performs a central role for tumor cells to regulate their metabolisms under hypoxia. Many genes are regulated by HIF-1 their expression will affect oxygen transportation, glucose uptake, glucolysis, and angiogenesis. Therefore, down regulation of the HIF system may interfere tumor's adaption to hypoxia, thus making it an attractive target for cancer therapy. As most regulations occur on the HIF-1 alpha subunit, researches focus on targeting HIF-1 alpha, which lead to the discovery of a variety of small molecular HIF-1 alpha inhibitors including camptothecin analogues, quinoxaline analogues, rapamycin analogues, some steroids, (aryloxyacetylamino) benzoic acid analogues and some naturally occurring substances like resveratrol and hesperidin. Here we summarize recent information on HIF-1 alpha, especially HIF-1 alpha inhibitors that have the potential of clinical usage.