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Cancer loves sugar. So much, that it is willing to be sloppy in the way that it makes energy just so it can gobble up more of the stuff. Lucky for us, this flaw is exploitable. We can use a machine called a "PET scanner" to watch where sugar goes in the body, and that can lead us right to a patient's cancer. Better yet, as scientists learn more about why cancer cells have such a love affair with the sweet stuff, we might be able to develop new treatments, too.

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PET is short for "positron emission tomography," and it can help doctors measure a whole bunch of different things, but it's often used to show where in the body cells are turning sugar into energy. It does this by detecting a radioactive substance that has been injected into a patient's bloodstream. One example is really similar to the sugar glucose, and it gets sucked up by sugar-hungry cells. And since cancer cells have the ultimate sweet tooth, they show up as bright blotches on a PET scan.

As you may or may not know, the reason why I keep wearing hats in SciShow videos is that I'm currently undergoing cancer treatment, so I go in for my PET scan, and it's a little freaky! Because they got, like, the thing they're going to inject in your veins in like, a lead-lined syringe to help protect the tech. Because they're, of course, going to get exposed to tons of it working for years... as radiation techs, but still. It's a little weird to have something that someone can't touch get injected into your veins. And then, I get the scan back, and it shows me exactly where the cancer is, and I'm like, "Yeah! Radiation in the cancer, that's great!" Then I also see that my brain is glowing like crazy, because the other place that consumes a lot of glucose is up here. [points to head]

So, that's roughly how it all goes down, but if you've had this experience, you might be wondering to yourself like I did, "Why does cancer like sugar so much?" And scientists would love to know that, too, because on the surface, this love affair doesn't make any sense.

See, cells produce and use energy mainly in the form of a molecule called "ATP" (adenosine triphosphate). Most of the time, healthy cells use oxygen to produce ATP from glucose through a series of biochemical reactions called "respiration." Now, respiration actually happens in a series of steps, the first one being glycolysis, where is turned into two of a smaller molecule called "pyruvate" and two molecules of something called "NADH."

Pyruvate can then be broken down further to make energy in one of two ways. First, when there's enough oxygen around, pyruvate undergoes the complex process of oxidative phosphorylation, where the mitochondria convert it into energy. We're going to refer to that one just as "respiration" for convenience to make things easier to follow. The alternative to respiration happens when there's not a lot of oxygen around. You still start with glycolysis, but after that, pyruvate takes an alternative route called "fermentation," where it's broken down less completely for less energy.

Respiration is great because cells can make a lot of energy through glycolysis plus oxidative phosphorylation. Fermentation is okay, too, because cells can still get the energy they need, but it is less efficient. Cells only get around 6% of the energy per unit of glucose from fermentation compared to respiration. Cancer cells have, for some strange reason, switched most of their energy-making to fermentation, even though there's plenty of oxygen around. They're still doing that first step - glycolysis - and some of that pyruvate goes through the respiration pathway, but somewhere between 56 and 63% of the ATP cancer cells make comes from fermentation. Researchers also call this kind of fermentation "aerobic glycolysis" to point out that this kind of energy-making *is* happening *with* oxygen.

And since fermentation is less efficient, cancer cells take up more and more sugar to get the energy they need. There's even a name for cancer's sugar obsession; it's known as the "Warburg effect" after the scientist who discovered it. And although it might seem totally odd, around 70-80% of human cancers get their energy this way. Warburg noted that it might be because the mitochondria - the parts of the cell that carry out respiration - become damaged in cancer cells. But it turns out the mitochondria are not only surviving, they are thriving. Plus, cancer cells aren't the only ones that use aerobic glycolysis; some, but not all, healthy human cells that multiply rapidly do the same thing.

So, researchers think there must be another reason. Now, one theory is speed; aerobic glycolysis is between 10-100x faster at making energy than respiration, which makes up for the fact that the process is so inefficient, providing there's enough glucose to go around. But cells, including cancer cells, have all kinds of other ways of making energy speedily, so it's weird that most cancers would choose this one way. And dividing and growing new cells actually doesn't take that much energy, at least not so much that a cell would need to resort to desperate measures just to make energy quickly.

Another explanation is that cells have other needs than just energy. They also need to make all the stuff that becomes all the parts of a new cell. A dividing cell needs to make more stuff: DNA, proteins, membranes - everything - otherwise, you just get two new half-sized cells. In 2021, researchers proposed a molecule that I have mentioned here, NADH, might actually play an important part - more specifically, it's counterpart: NAD+. The NAD+ has many rules in the cell, including helping make all that stuff a new cell needs. But it's also involved in both halves of the energy-making pathway, respiration and fermentation.

Remember how I said that after the first step of energy-making, glycolysis, you get a few molecules of NADH? NAD+ and NADH cycle between their two forms by either gaining or losing electrons. And when they do, they help create energy. But at the end of both fermentation and respiration, NADH is turned back into NAD+, so the whole thing can start over again, and the cell can metabolize more glucose.

But for cancer, say the researchers in that 2021 paper, there's a catch. In the process of respiration, the amounts of ATP and NAD+ you get at the end are linked; so if you want to make more of one, you also got to make more of the other. That means if a cell needs more NAD+ relative to ATP - say, if it needs break down lots of glucose or make lots of stuff - then regular respiration actually *isn't* the best way to go. Instead, it makes more sense for the cell to use fermentation to get a little more NAD+ back at the end of it.

Now, we did not need to understand the complex biochemistry behind cancer cell's sugar crush to exploit that fact for PET scans, but it might just help researchers develop better cancer treatments. Now, it's not as simple as just not eating sugar; our bodies are really good at getting glucose into the bloodstream, because that's how all of the cells work. This is a bit of a myth of the alternative cancer treatment space based on oversimplifying how all this complicated energy metabolism stuff works. But one idea is to suppress tumor growth by tapping into some of those metabolic pathways and limiting how much of that stuff cancer cells can make.

Of course, like all things cancer, tumors are complex beasts, and there's never going to be a one-size-fits-all answer. But every time we find a one-size-fits-some solution, those people's lives get so much better.

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