Scientists running down another blind alley

Cancer is a disease that simply must be prevented. Once it appears, it is bad news. Cures resemble miracles because generally the very appearance of a sizable tumor in the body means that the body, which has already lost numerous battles fighting it, is already too weak to beat it. Strengthening the body by essentially reversing the wrong course (more precisely keeping a little of what one has been doing [because it was not TOTALLY WRONG] while adding a large dose of the reverse course) one has traveled is still more likely the best way to fight cancer.
Keeping the body strong throughout one’s lifetime should have been and still could be the focus if sense ever triumphs among scientists. This would require scientists to shift their focus from the cure of disease to maintenance of health (and the prevention of disease), something Weston Price did many years ago.
The pharmaceutical approach, using inappropriately high concentrations of drugs, singly or in combination, to solve problems, is bankrupt. It is a bad idea. Nature makes no use of it because nature found a better way by natural selection: use a network of molecules to solve problems, each at a concentration well below maximum allowable concentration, to achieve the effect with maximum S/N, signal to noise ratio. Maximum S/N is never at maximum S.
Now scientists want to test injection of massive quantities of oxidized vitamin C to combat a minority of cancers that both over-rely on glucose as an energy source and have one of two particular mutations. This will select for tumor cells that also use other energy sources such as alanine and glutamine. It will also have side effects, as oxidized vitamin C is a dangerous substance that the body does not keep around – the body quickly reduces – using its antioxidant network- what little oxidized vitamin C is produced (by reducing oxidized vitamin E in membranes) by using glutathione, which is in turn quickly reduced by glutathione reductase, which is quickly re-powered by regenerating NADPH, the ultimate cellular antioxidant, from the oxidation of foodstuffs for fuel.
Here is the article:
Vitamin C kills tumor cells with hard-to-treat mutation

Maybe Linus Pauling was on to something after all. Decades ago the Nobel Prize–winning chemist was relegated to the fringes of medicine after championing the idea that vitamin C could combat a host of illnesses, including cancer. Now, a study published online today in Science reports that vitamin C can kill tumor cells that carry a common cancer-causing mutation and—in mice—can curb the growth of tumors with the mutation.

If the findings hold up in people, researchers may have found a way to treat a large swath of tumors that has lacked effective drugs. “This [could] be one answer to the question everybody’s striving for,” says molecular biologist Channing Der of the University of North Carolina, Chapel Hill, one of many researchers trying to target cancers with the mutation. The study is also gratifying for the handful of researchers pursuing vitamin C, or ascorbic acid, as a cancer drug. “I’m encouraged. Maybe people will finally pay attention,” says vitamin C researcher Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases.

In 1971, Pauling began collaborating with a Scottish physician who had reported success treating cancer patients with vitamin C. But the failure of two clinical trials of vitamin C pills, conducted in the late 1970s and early 1980s at the Mayo Clinic in Rochester, Minnesota, dampened enthusiasm for Pauling’s idea. Studies by Levine’s group later suggested that the vitamin must be given intravenously to reach doses high enough to kill cancer cells. A few small trials in the past 5 years—for pancreatic and ovarian cancer—hinted that IV vitamin C treatment combined with chemotherapy can extend cancer survival. But doubters were not swayed. “The atmosphere was poisoned” by the earlier failures, Levine says.

A few years ago, Jihye Yun, then a graduate student at Johns Hopkins University in Baltimore, Maryland, found that colon cancer cells whose growth is driven by mutations in the gene KRAS or a less commonly mutated gene, BRAF, make unusually large amounts of a protein that transports glucose across the cell membrane. The transporter, GLUT1, supplies the cells with the high levels of glucose they need to survive. GLUT1 also transports the oxidized form of vitamin C, dehydroascorbic acid (DHA), into the cell, bad news for cancer cells, because Yun found that DHA can deplete a cell’s supply of a chemical that sops up free radicals. Because free radicals can harm a cell in various ways, the finding suggested “a vulnerability” if the cells were flooded with DHA, says Lewis Cantley at Weill Cornell Medicine in New York City, where Yun is now a postdoc.

Cantley’s lab and collaborators found that large doses of vitamin C did indeed kill cultured colon cancer cells with BRAF or KRAS mutations by raising free radical levels, which in turn inactivate an enzyme needed to metabolize glucose, depriving the cells of energy. Then they gave daily high dose injections—equivalent to a person eating 300 oranges—to mice engineered to develop KRAS-driven colon tumors. The mice developed fewer and smaller colon tumors compared with control mice.

Cantley hopes to soon start clinical trials that will select cancer patients based on KRAS or BRAF mutations and possibly GLUT1 status. His group’s new study “tells you who should get the drug and who shouldn’t,” he says. Cancer geneticist Bert Vogelstein of Johns Hopkins University, in whose lab Yun noticed the GLUT1 connection, is excited about vitamin C therapy, not only as a possible treatment for KRAS-mutated colon tumors, which make up about 40% of all colon cancers, but also for pancreatic cancer, a typically lethal cancer driven by KRAS. “No KRAS-targeted therapeutics have emerged despite decades of effort and hundreds of millions of dollars [spent] by both industry and academia,” Vogelstein says.

Others caution that the effects seen in mice may not hold up in humans. But because high dose vitamin C is already known to be safe, says cancer researcher Vuk Stambolic of the University of Toronto in Canada, oncologists “can quickly move forward in the clinic.”

One drawback is that patients will have to come into a clinic for vitamin C infusions, ideally every few days for months, because vitamin C seems to take that long to kill cancer cells, Levine notes. But Cantley says it may be possible to make an oral formulation that reaches high doses in the blood—which may be one way to get companies interested in sponsoring trials.

Posted in Chemistry, Health


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