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March 4, 2005

Overexpression of Hypoxia-inducible Factor 1{alpha} in Common Human Cancers and Their Metastases

Topics: Medicine

Several readers have emailed me asking about the role of oxygen in tumorigenesis and cancer treatment, and whether or not there was any truth to a possible role of angiogenesis inhibitors in human cancer. For those readers and others among you who are interested in this topic, the following is offered in the way of thought-invoking material:

Altered glucose metabolism and cellular adaptation to hypoxia (lowered oxygen concentration) are fundamental to the basic biology and treatment of cancer. Four lines of evidence support this thesis: (a) clonal expansion of cancer cells depends on enhanced glucose transport and glycolysis (the Warburg effect); (b) tumors cannot grow beyond several mm3 without angiogenesis (development of a new blood supply) because of the limited diffusion of O2, glucose, and other nutrients.

In many cancers, the degree of vascularization is inversely correlated with patient survival; (c) the probability of invasion, metastasis, and death are positively correlated with the degree of intratumoral hypoxia , which is caused by an architecturally defective microcirculation such that even cells adjacent to neovessels may be hypoxic. Cancer cell proliferation may also outpace the rate of angiogenesis ; and (d) tumor hypoxia is associated with resistance to chemotherapy, immunotherapy, and radiotherapy .

Despite the critical importance of these observations, their molecular basis is not well understood, and transcription factors that regulate expression of angiogenic growth factors (such as VEGF - vascular endothelial growth factor) or glycolytic enzymes involved in the Warburg effect, are compelling targets for interrogation. HIF-1 performs both of these functions.

Continue reading about this very interesting topic, and yes, the role of oxygen(particularly the lack of it) in human cancer, is well established.

Posted by Hyscience at March 4, 2005 1:01 PM

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