Is it true that cancer feeds on sugar?

Answer by Jeffrey Nguyen:

All the answers given so far are generally correct, but they are not complete. Cancer cells do indeed use sugars, specifically glucose, to create energy in the form of ATP; however, cancer cells depend more on glucose than normal cells do due to what is known as the Warburg Effect.

First, let me back up, recap, and summarize the answers that have been given so far to answer some of your questions. In summary, all normal cells use glucose a source of energy. Glucose is metabolized by the cell through a series of reactions, which can be divided into three parts: glycolysis, the Krebs cycle, followed by the electron transport chain located within the mitochondria. The result of these reactions converts one glucose molecule into ~30 molecules of ATP, which is the energy currency that cells use for most of their cellular processes. During extreme conditions (ie starvation), when the a cell goes through their glucose stores, they can use fats and protein as an energy source, but it is not ideal. This is why if you have ever seen people that have been lost in the wilderness after a long time, their body has wasted away. In an attempt to survive, their body first when through all their sugar/glucose stores, followed by their fat and protein stores, causing them to become emaciated. Someone also mentioned that glucose/sugars, along with proteins are important cellular components. Indeed, all the four types of macromolecules (proteins, lipids, sugars, and nucleic acids) are important cellular components. Most people know proteins are a structural component of the cell, and they are probably most familiar with this concept in the context of bodybuilding where protein allows bodybuilders to increase muscle mass. Proteins also have roles beyond structure components – they pretty much carry out almost all the functions of the cell; whereas the other macromolecules have primarily a structural or energy/information storage roles (lipids for cell membranes, sugars for energy and protein/lipid modifications, and nuclei acids for information storage), proteins primarily have a functional role – they do stuff.

One would assume that cancer cells, having been derived from normal cells, also follow this same energy requirement heirarchy, but actually it’s a little different. As another poster mentioned, a simple definition of cancer is the abnormal proliferation of cells; this proliferation is mainly due to an accumulation of genetic mutations that allows a cell to forego the normal checks and balances that keeps normal cells proliferating in a controlled, regulated fashion. As a result of these genetic mutations, however, cells acquire phenotypes that are characteristics of almost all cancers. A nice diagram of this is shown below.

I don’t know why the picture duplicated, but those 10 phenotypes are also known as “the hallmarks of cancer.” Notice in the top left corner that one of the phenotypes is “deregulated energetics.” This is where the Warburg effect comes in.

The buildup of genetic mutations that allows cells to abnormally proliferate, also alters the expression of proteins involved in energy metabolism, specifically glucose metabolism. The net result is that the Krebs cycle and mitochondrial phases of glucose metabolism shut down, and the cell becomes heavily reliant on glycolysis for energy. There are a couple thoughts on the evolutionary rationale for why this occurs: 1) speed: ATP can be produced at a faster rate by relying only on glycolysis, even though by going through glycolysis/krebs/etc would produce more total ATP from one glucose molecule; the proliferative demands of a cancer cell translates to increase energy demands, so the speed of glycosis is favored over efficiency 2) the increased proliferative demands also creates a greater biosynthetic demand: cells that are proliferating need to duplicate all the cellular components with each proliferation; this greater biosynthetic demand means that the cell needs more building blocks for all the macromolecules of the cell. These building blocks, in turn, are produced from certain metabolic precursors and glycolysis produces these metabolic precursors. The net result is that cancer cells rely predominately on glycolysis to produce energy, which makes them particularly dependent on glucose. This phenomenon is called The Warburg Effect.

An an example of this phenomenon in action, if you are someone you know is in the unfortunate position of being suspected of having advanced cancer (ie cancer that has metastasized), you may have ingested 2-18F-2-deoxyglucose. This is a modified glucose that has a radioactive fluorine that can be detetected by a PET scan. As a result, if you are a patient with advanced cancer with metastatic deposits all over your body, your cancer cells will preferentially take up this glucose and will light up like a light bulb, like this:

It seems to have duplicated again. Anywho, in A you can see black dots everywhere. Those are sites where there are cancer cells. The one area that is an exception is the black triangle in the pelvic area – that is the bladder. The bladder lights up due to radioactive glucose building up in the bladder after having been filtered by the kidneys. In panel B, it looks like an image post-chemo, since you can see the black spots have disappeared. Unfortunately, in C is looks like the cancer has recurred.

The protein mainly responsible for the Warburg effect is an isoform of pyruvate kinase, M2. Pyruvate kinase is the glycolytic enzyme that peforms the last step in glycolysis. As it turns out, cancer cells overexpress this M2 isoform of pyruvate kinase, which drives the increased rate of glycosis that is characteristic of tumor cells. Developing inhibitors for this special isoform of pyruvate kinase along with glycolytic inhibitors (inhibitors of glycolysis) is an active area of research. Finally, one poster mentioned the ketogenic diet as a potential last-ditch treatment for cancer. Interestingly, according to Wikipedia, as of 2013, there is enough anecdotal evidence of the potential for use of the ketogenic diet in cancer treatment, but clinical trials have not been performed yet. See Ketogenic diet

Finally, I don’t know if any studies have shown a correlation between dietary sugar consumption and metastatic cancer, so I don’t think we can conclude that “sugar fuels the spread of cancer cells.”

Is it true that cancer feeds on sugar?