Exploitation of the HIF axis for cancer therapy.
Hypoxia, a reduction in the normal level of tissue oxygen tension, occurs in most solid tumors in regions where tumor growth outstrips new blood vessel formation. Hypoxic cancer cells are resistant to both chemotherapy and radiation and are a major reason for the failure of cancer therapy. The cellular response to hypoxia is mediated through the hypoxia-inducible transcription factor-1 (HIF-1). HIF-1 is critically important for tumor progression and angiogenesis. In fact, HIF-1alpha is overexpressed in 70% of human cancers and their metastases. Thus, agents that inhibit angiogenesis and tumor growth via inhibition of HIF-1 represent an attractive yet unexplored new modality for cancer treatment. We will overview inhibitors of HIF-1alpha and will discuss their potential use for cancer therapy.
Escuin
Daniel
D
Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
Simons
Jonathan W
JW
Giannakakou
Paraskevi
P
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors