Why cancer cells waste so much energy

If cancer cells have high metabolic requirements, couldn't you attack them by:...

The keto diet is actually recommended for certain types of cancer patients for this reason. While almost all human body cells can adjust to using ketones, most types of cancer cells cannot.

Great questions.

1. We do attempt to attack cancers by reducing their available energy. That's why, at one point, a major field of research in cancer therapeutics was interfering with angiogenesis, because cancers will secrete messengers that help grow them dedicated (if crappy, low-quality) blood vessels. The issue with "starving" them more starkly is that they're very good at getting a share (e.g., forcing the body to supply them with blood vessels), so you're going to be hitting other labile tissues as fast or faster (skin, GI mucosa, blood and immune cells.)

Another way of targeting their rapid metabolism is pointing our therapy at cells with high replication rates. A number of our cancer therapeutics are aimed directly at cells that are currently replicating, which should selectively hit cancer cells (though again, it hits skin, GI mucosa, blood and immune cells, etc. because they're also high-turnover cells.)

We use methotrexate to interfere with DNA synthesis, thus reducing the rate of replication altogether (in cancer cells, as well as.... above).

The problem is, besides the dose-limiting toxicities of all of these things (because targeting metabolism hits all high-metabolism cells), is that cancer cells are really good at developing resistances. So, for instance, if you starve them of blood supply, they'll switch to anaerobic metabolism of glucose. If you starve them of glucose, well, you can't really - I'll discuss that below. If you give them methotrexate or other nasty drugs, they alter the cells' native drug-efflux pumps to target those drugs better and pump them right out of the cell. Cancer cells have a broken mechanism for protecting DNA - the result is really high rates of cell death among cancer cells, and also really rapid evolution.

In terms of starving cells of glucose: glucose is the least common denominator of cellular metabolism. It's the primary food source for the brain. Different cells have different receptors for absorbing it, with different levels of affinity. If you're running low, pretty much every cell in the body that can will kick up metabolic products to the liver to turn into glucose it can share with the bloodstream - because the best receptors in the bloodstream for picking up glucose belong to the brain. You'll starve, or poison, the brain long before you manage to starve out a cancer. (Yes, Ketone bodies are a thing, but that happens alongside your body mobilizing everything it can to feed the brain, not instead of.)

We also can't 'see' all the tumor. The way cancers actually develop is you have an abnormal cell A, which grows into a tiny nest. These are below detection in any practical clinical way, and we don't want to treat them because they're ridiculously common - your immune system wipes them up. If we tried to detect and treat them all, we'd kill everyone with side effects long before we prevented a fatal cancer.

Out of the bunches of these that develop and die, or develop and go permanently quiet, one gets active enough to start seeding tumor cells into the blood stream. Most of those cells will die, too, because blood is rough for cells not built to withstand it. Most of these are going to be undetectable in any way, and do nothing to people.

(Every time I say something is undetectable, I mean "Except for high precision laboratory experiments used to detect just such things").

Eventually a tiny pre-pre-tumor will start seeding cells into the blood stream that can survive the blood. These will get seeded effing everywhere. Most of these are permanently quiescent and do nothing, ever. They exist at the level of single cells - we can't see them. They don't do anything, metabolic activity very low, so we can't target them.

Once in a blue moon you get one seeded that is actually metabolically highly active. Or maybe it mutates into metabolic activity later. Most of those die.

Once in a blue moon, one of these will live enough to start replicating for real. Most of those get wiped out.

And once in a blue moon, they start replicating for real, and develop immune evasion, and you have something that becomes a cancer, maybe. Or it gets triggered by something external and becomes a cancer. There's a "seed and soil" element here. It'll often start seeding back into the blood stream.

By the time you have a detectable mass, your entire body has been seeded with these cells, most of them both un-image-able and un-selectively-treatable. Luckily, the overwhelming majority of these cells - lots of nines - won't do jack. Of the trillions that will seed your body, if we stimulate them just right, you might get a couple of new tumors, or none at all.

We know this because we learned that tumors benefit from circulating inflammatory markers early in modern oncology. When a surgeon took out a tumor, not infrequently, a patient would come in a year later with a new one or two that weren't previously detectable. We eventually learned that the inflammatory growth signals that come with surgical trauma can provoke an otherwise sleepy tumor cell into metabolic activity.

Which is a roundabout way of saying "cancers are more metabolically varied than the late, aggressive stage of the process we usually refer to as 'cancer' would suggest."

That being said, if you could inject something directly into the tumor (rather than the bloodstream would prioritize sending said poison pill glucose to the brain or liver) and take advantage of its metabolism, that would be great. We do kind of do that: we implant radioactive pellets directly, with the added benefit that we know it won't affect much tissue outside of the immediate area.

I hope my answer was actually useful in providing some biological context? I'm afraid I might have just word-vomited instead of being helpful.

I'm not sure how detectable fasting during daylight hours 10% of the year would be. I'm thinking other confounding factors (like massive amount of fructose in diet driving obesity levels) in western countries would swamp that out. Not to mention the Ramadan fast is only a modest form of intermittent fasting. The caloric intake for the day is quite high, often higher than normal due to feasting, and the hours of fasting are anything from 12-18 (while eating once a day would be more like a consistent 21h of fasting year round).

Here is an NCBI article about the Warburg effect that I found illuminating

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/

Does the difference in metabolic pathway lead to e.g. different waste products present in the blood?

I.e. could you do a blood test to detect elevated levels of fermentation-based metabolism, indicating that it might be time to do a deeper cancer screen?