Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies.
Human solid tumours are considerably less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy, as well as predisposing to increased tumour metastases. However, tumour hypoxia can be exploited in cancer treatment. One such strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise. The second way to exploit hypoxia is to take advantage of the selective induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) under hypoxic conditions; gene therapy strategies based on this are in development.
Brown
J M
JM
Cancer Biology Research Laboratory, Stanford University Medical School, Stanford, CA 94305, USA. mbrown@leland.stanford.edu
D000880:Anthraquinones / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D015316:Genetic Therapy; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D009687:Nuclear Proteins / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D000077704:Tirapazamine; D014157:Transcription Factors / Q000378:metabolism*; D014227:Triazines / Q000737:chemistry / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000880:Anthraquinones; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D011838:Radiation-Sensitizing Agents; D014157:Transcription Factors; D014227:Triazines; D000077704:Tirapazamine; C094428:AQ4N