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Wednesday, July 25, 2012

Deoxyglucose and Cancer Treatment 

About thirty years ago I wrote this paper, based on work done in consultation with Japanese and other colleagues:

http://www.sciencedirect.com/science/article/pii/0305049183903127

This paper has had a steady citation rate since. What seems to have happened is that clinicians researching ways to starve glucose-guzzling cancers have hit on the idea of giving patients the glucose analogue, 2-deoxyglucose. This glucose analogue is not metabolised normally, and the idea is that the cancer cells will be especially badly affected by the 2-deoxyglucose because of their increased need for energy from glucose.

People cite our paper to indicate that there is in fact some metabolism of 2-deoxyglucose along the pentose phosphate pathway, with some energy captured in the form of NADPH. They cite our paper as evidence that the energy-starving effect of using 2-deoxyglucose, and hence its effect on energy-requiring cancer cells, may not be as great as one would expect if 2-deoxyglucose were not metabolised at all.

My concern with this is that our research was done on red blood cells. These cells do not have the citric acid cycle and oxidative phosphorylation. They do however have a very active pentose phosphate pathway, which, as we reported in our paper, is the pathway that 2-deoxyglucose follows in red blood cells. There is no guarantee that other cells, including the cancer cells being targeted by clinicians, will metabolise 2-deoxyglucose and produce energy equivalents to the same degree. In short, the clinicians may be being too cautious in their expectations. At the very least, our findings in red blood cells should be checked in other cells, most of which have quite different energy metabolism.


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