Dead cells don't form tumors: HIF-dependent cytotoxins.
Elimination or reduction of tumor burden is the primary goal of cancer therapy. Strategies to achieve this goal with the fewest adverse effects to the patient are an area of intense investigation. Elevated protein levels of hypoxia-inducible factor (HIF) are commonly found in solid tumors, while rarely found in healthy tissue. Numerous studies have suggested that HIF activity is essential for the development of solid tumors. Thus, inhibition of HIF represents an attractive therapeutic target for eradicating tumors. The search for small molecules that target and inhibit HIF activity is currently underway. We propose an alternate approach: to directly target and kill HIF-activated tumor cells. This approach is advantageous in that cells with activated HIF will be eliminated directly. Specific elimination of HIF-activated cells represents a potential mechanism for inhibiting tumor growth, with the potential advantage of sparing the patient of the normal tissue toxicity associated with current treatment options.
Sutphin
Patrick D
PD
Program in Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, California 94305-5787, USA.
Chan
Denise A
DA
Giaccia
Amato J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D016923:Cell Death / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003603:Cytotoxins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008958:Models, Molecular; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein
C497396:ARNT protein, human; D000970:Antineoplastic Agents; C497397:Arnt protein, mouse; D003603:Cytotoxins; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D018336:Receptors, Aryl Hydrocarbon; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D010100:Oxygen; D020123:Sirolimus