Targeting the molecular basis for tumour hypoxia.
Tumour hypoxia stems from impaired oxygen delivery as a result of a disorganised tumour vasculature and inadequate blood supply. Hypoxic tumours are highly resistant to chemotherapy and radiation therapy and correlate with a poor patient prognosis. Hypoxia is a powerful stimulus for the expression of genes involved in cell survival and angiogenesis. A key factor in this process is hypoxia-inducible factor (HIF), which regulates transcription of hypoxia-activated genes. Efforts are currently under way to develop targeted cancer therapeutics to hypoxia-activated pathways, and in particular to the transcription factor HIF.
Carroll
Veronica A
VA
Cell Growth Regulation and Angiogenesis Laboratory, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK. veronica.carroll@icr.ac.uk
Ashcroft
Margaret
M
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011355:Prodrugs / Q000493:pharmacokinetics; D017434:Protein Structure, Tertiary; D011836:Radiation Tolerance
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D011355:Prodrugs