important discovery from Harvard --leading to new selective targeting of cancer

[CLTann]

Further thought on the subject.

If glucose is the culprit in the disease process, as the article implies, I am wondering how can anyone avoid to have this life supporting intermediate in one's system. As we all know, all foods go through our body and convert into glucose. Then, how could any experiments be conducted while maintaining the nutrition requirement of the animals?

Ann

[Christine MH-UK]

There has been some very promising work on mice using 3-bromopyruvate, which interferes with glycosis in liver cancer, and this article I just found on the internet from the May 2006 edition of Science Magazine mentions a few others that interfere with the energy dynamics in cancer cells. These drugs are at various stages of development, including some already in clinical trials. At one point it quotes two scientists who say that glycosis seems to be a factor in the survival of tumors rather than the origins of tumors. Unfortunately, it also makes clear that not all cancers are glycolytic, only about 60% to 90%, so won't cure all cancer patients, even if it works really well.


http://www.usuhs.mil/alumni/energydereg.pdf

[MJo]

"If glucose is the culprit in the disease process, as the article implies, I am wondering how can anyone avoid to have this life supporting intermediate in one's system."

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I'm wondering too, since I already live without estrogen. LOL. MJO

[Christine MH-UK]

This is from the Science article and shows how drugs might use a cancer cell's dependence on glycolysis against it. I have highlighted a sentence that I think is very important, since it shows that they are trying to find substances that make it difficult for cells to use glucose.

"Drugs targeting tumor bioenergetics are on the way. Most exploit a tumor's increased reliance on glycolysis. Threshold Pharmaceuticals Inc., a biotech company in South San Francisco, California,is already testing two such drugs in cancer patients: a chemotherapy compound conjugated to glucose, and a glucose analog that cannot be metabolized, thus shutting down glycolysis. Hexokinase, because it catalyzes the first step in glycolysis and can block cell death, is another key target. Hay, for example, proposes that drugs causing hexokinase to separate from mitochondria could treat cancer, by both damping down glycolysis, indirectly blocking a signaling enzyme is another strategy. In 2004, Johns Hopkins researchers reported that a hexokinase inhibitor, 3-bromopyruvate, completely eradicated advanced glycolytic tumors in all mice treated. Chemists at the M. D. Anderson Cancer Center in Houston, Texas, are now developing 3-bromopyruvate analogs for eventual clinical trials. Other potential drug targets exist. Last year, Thompson identified an enzyme, ATP citrate lyase, that allows cancer cells to overcome a natural check on glycolysis. Inhibiting it blocks growth of tumors in mice. And this March, Dang and Nicholas Denko of Stanford University in California separately reported that another enzyme, pyruvate dehydrogenase kinase (PDK), acts to shut down mitochondrial respiration and protect cells in low-oxygen conditions. "One can imagine that by blocking PDK activity we can actually trigger cells to commit suicide," Dang says. Compounds that limit glycolysis would, in theory, kill cancer cells while sparing normal cells, which can burn amino acids and fatty acids for energy. "When [cancer] cells are engaged in highthroughput aerobic glycolysis, they become addicted to glucose," says Thompson. "So if you suddenly take away their ability to do high-throughput glucose capture and metabolism, the cell has no choice but to die.""