The New York Times published a major article on the possibility of curing cancer by starving cancer cells to death (NYT, May 12, 2016), a theory first proposed almost 100 years ago by Otto Warburg, arguably the world’s greatest chemist ever. With the discovery of the structure of DNA by Watson and Crick more than 50 years ago, scientists diverted their attention to a genetic basis for cancer research. However, it now appears that most cancers are influenced by environmental factors (Carcinogenesis. March, 2014;35(3):515-27). Once again scientists are doing solid research based on Warburg’s ideas that cancer could be both prevented and cured by depriving cancer cells of sugar. We know that cancer cells die without sugar; the challenge is finding a way to target the cancer cells without also depriving normal cells of sugar.
How Cancer Cells Differ from Normal Cells
Every normal cell (except mature red blood cells) contains a few to thousands of little compartments called mitochondria that efficiently convert food into energy. Normal cells get their energy from two main sources:
• inside the mitochondria, from fat, sugar and protein in the Krebs Cycle
• outside of the mitochondria, but still inside the cell, from sugar by glycolysis
Cancer cells have defective mitochondria, so they must get most of their energy from sugar by glycolysis.
The DNA in a normal cell forces it to undergo apoptosis, which means that the cell doubles a set number of times and then dies. Red blood cells live 120 days and then die, skin cells live 28 days and then die, while the cells lining your mouth live only two days and then die. Because the DNA in cancer cells is damaged, they do not have apoptosis, so they try to live forever and they become so numerous that they overrun other tissues. For example, breast cancer cells do not kill until they travel to and destroy the brain, liver, bones, lungs and so forth.
Research on Sugar and Cancer
We know that there is a strong association between excess sugar intake and increased cancer risk. Everything that causes high rises in blood sugar increases risk for developing cancers: diabetes, lack of exercise, obesity (particularly abdominal obesity), eating a lot of animal fats (blocks insulin receptors), not eating lots of fruits and vegetables, not eating lots of fiber and so forth. Researchers are making important strides to explain the association:
• Chi Van Dang, of the University of Pennsylvania, has shown that the MYC gene turns normal cells into cancerous ones by causing them to take up large amounts of sugar and use it for energy both with and without needing oxygen. Cancer cells have defective mitochondria that prevents them from having a normal Krebs Cycle, so they have to get most of their energy from sugar to supply them with energy.
• Craig Thompson, of the Memorial Sloan Kettering Cancer Center, has shown that defective AKT proteins block apoptosis to cause cancer. AKT proteins that are supposed to send signals from one cell to another fail to do their job of telling cells when to die.
• Excess sugar intake causes cancer by pathways called EPAC/RAP1 and O-GlcNAc (J Clin Invest, Jan 2, 2014;124(1):367–384; Sci STKE, 2006;346re7).
• Preventing sugar from getting into cancer cells shrinks solid tumors. Peter Pedersen of Johns Hopkins has shown that 3-bromopyruvate can stop liver cancers from growing by blocking their sources of energy. These studies were done in a laboratory, not in humans.
• Reviving mitochondria in cancer cells can shrink established cancers. Dichloroacetate (DCA) activates mitochondria to shrink lung, breast and brain cancers in rats (Science Translational Medicine, May 12, 2010;2(31):31ra34); however, drug companies are not interested in DCA because it cannot be patented.
• Several studies have shown that metformin (Glucophage), a common drug used to lower blood sugar and insulin in diabetics, helps to prevent cancers and to shrink cancers that have already started (Ann Transl Med, June 2014;2(6):57).
More and more scientists are coming to recognize that Otto Warburg may have predicted a way to cure cancer almost 100 years ago. I believe that in the near future, cancer will be prevented and cured by keeping cancer cells from meeting their needs for energy, primarily by blocking sugar uptake into cancer cells. I have written about his exciting research several times in the last few years, and will continue to follow it closely: