Y’know cancer? It’s basically communism for your cells. Your cells work away their entire lives just so the sperm/egg bourgeoisie can do nothing but laze around all day and maybe have sex. But do the proletariat ever get to taste the fruits of their own labor and pass on their genes to the next generation? No. They die when you die. 

But then Oncovirus Marx publishes the Cancerist Manifesto directly into the genomes of the proletariat. The workers of the body rise up and seize the means of reproduction! They evade prosecution by the immune system police and begin dividing without control.

They establish a tumor regime, which mismanages resources resulting in millions of cells starving to death, but they still manage to spread through the whole body. The immune system and doctors get bogged down in self destructive conflicts trying to contain it. Then the cancer inevitably collapses under its own weight taking the whole body with it in an act of mutually assured destruction.

Well, it turns out that many types of cancer aren’t so much Marxist as they are Stalinist, which is to say there’s an elite group of cancer cells who are “more equal” than others. 

Maybe not quite Stalinist; most historians do not believe that Joseph Stalin was able to survive chemical weapons and nuclear fallout, live forever unaging, then rebuild the Soviet Union single handedly by giving birth to legions of specialized laborers and copies of himself. So a better comparison would be North Korea, as of course, Supreme Leader Kim Jong-un senpai is fully capable of all these feats and more. Probably.

Contents:

• Cancer is Complicated
• Why Stem Cells are at a Higher Cancer Risk
• Origin of Cancer Stem Cells
• Immortal Cancer
• Resistance
• Chemo and Radiation Resistance
• Toxin Resistance
• Death Resistance

Cancer is More Complicated than We Thought

Ever wonder why we still haven’t cured cancer? It’s to the point where it’s almost become a running joke. Well, it’s the same as saying you’ll “fix” your relationship issues. It’s complicated. 

Not only are there multiple types of cancer, but there’s also multiple types of cancer cells. Cancer Stem Cells (CSCs) are rare cancer cells found inside tumors that exhibit stem cell like properties. When I say rare, I mean that any given tumor is probably less than 5% CSCs. But it’s thought that most malignant tumors contain a core of CSCs which are the primary force driving cancer progression.

CSCs have a number of special abilities. Notably, they are able to make a whole lot of other normal cancer cell types creating tumors, make more of themselves so the tumor doesn’t run out, leave and travel through the body to build new tumors, enter dormant states, be biologically immortal, and be highly resistant to cancer drugs. So yeah, they’re kind of a big problem.

You may have heard of stem cells. If all you know about them is that they come from babies, don’t worry. We can get them from adults now, too. They’re cells that can turn into other types of cells and are really good at healing and even regenerating the body. 

Cancer Risk

Y’know how lizards can regrow parts of their body? They use stem cells for that. We can’t regrow our limbs because we don’t have very many stem cells, which is probably a good thing. Stem cells are at higher risk of becoming cancerous. 

Lizards don’t have to worry about that because they’re so small. They don’t need that many stem cells. Fewer cells means a lower chance of one becoming cancerous. 

Larger animals, like Humans, have trillions of cells and need to evolve more countermeasures to compensate. Apparently, evolution decided that keeping that many stem cells weren’t worth the risk.

Origin of Cancer Stem Cells

Given the name you’d probably guess that cancer stem cells are just cancerous stem cells. In many cases, you’d be right. Nearly any cell type can become cancerous, and that includes stem cells.

But CSCs often arise from normal cancer cells which, through clonal evolution, have unlocked traits associated with stem cells because each of these traits happen to be evolutionarily advantageous to the individual cancer cell. 

Yes, cancer can evolve. Cancer cells are highly mutagenic and have very short generation lengths, so they evolve relatively quickly. But most of that just comes from them unlocking genes already present in the genome but aren’t normally allowed to use. Imagine if some caveman found an “EMERGENCY MACHINE GUN, IN CASE OF EMERGENCY BREAK GLASS” box. They’ll probably start progressing a lot faster than they would have just from banging rocks together.

Immortal Cancer

Remember in my articles about aging where I talk about senescence and telomeres? Basically, every time a cell divides it loses a bit of DNA off the end of its chromosomes. There are caps of otherwise unused DNA called telomeres that get cut off instead, but after enough divisions, even this is lost and any further divisions would start to cut into actually important genes. So cells usually just stop dividing at that point, causing senescence and aging. 

Healthy stem cells are able to regenerate their telomeres making them effectively immortal and mostly immune to aging. This is good because stem cells need to divide more than any other cell type in the body.

Well, it turns out that maybe the reason why we evolved to lose our telomeres in most cells is actually a defense against cancer. If a normal cell becomes cancerous and starts dividing rapidly, as cancer does, it will quickly wear through its telomeres and destroy its own DNA. Hence why nearly all the cancers we see can regenerate their telomeres and are immortal. The ones who don’t mutate that ability die of age before we even notice them.

Evolution’s solution for cancer is multilayered defense. There are numerous oncogenes that encode for various defenses, any one of which can single handedly stop cancer in its tracks. (There are also many which only hinder cancer, not stop it, but my point is there are multiple genes that can fully stop it.) 

Hence, in order for cancer to become dangerous a single cell will need to have collected enough mutations to deactivate every single one of these defenses, the chances of that happening are astronomically low. This is why, even though you have trillions of cells, you still have a good chance of living a full life without any of them developing into malignant tumors.

But stem cells already have some of these defense mechanisms turned off by default! So stem cells are at a greater risk of becoming cancerous.

CSC resistance

CSCs are particularly resistant to treatment through several mechanisms.

This may be part of why chemotherapy, immunotherapy, and targeted therapies are often not enough to cure cancer. The CSCs inside tumors must be physically destroyed with surgery or intense radiation exposure. 

Even if a targeted therapy drug has shown effectiveness against normal cancer cells, they may not be as effective against CSCs. Even if therapy eradicates all normal cancer cells, surviving CSCs can still regrow the tumor.

Resistance to Chemo and Radiation

Chemotherapy and radiation therapy specifically kill cells as they are dividing. Hence, it disproportionately harms the fastest growing cells in your body. 

Unfortunately, cancer cells aren’t the only fast dividing cells, there’s also cells that grow hair, stomach and intestinal lining, bone marrow, germ cells, etc. So this explains the other side effects of chemotherapy such as hair loss, slowed rate of healing, low blood cell count, infertility, digestive issues, etc. But, all going well, you can survive without those things longer than cancer can survive without cancer cells. And you can usually make a full recovery from the effects of chemotherapy.

So while chemotherapy is very good at killing most cancer cells with completely unmoderated division, CSCs are more resistant. Cancer stem cells tend to divide slower than normal cancer cells. They can also enter dormancy states where they don’t divide at all, which apparently is something normal stem cells also like doing. 

Protein Pumps

Proteins are remarkable in their ability to create tiny molecular machines. One of the most common forms of this are “pumps”. 

Imagine you’re on a sinking ship that is slowly flooding, and you don’t feel like going for a swim right now. How could you possibly prevent this? Prevent the ship from losing buoyancy! So you take out a powerful pump you happen to have that can pump the water back out just as fast as it leaks in. While it would technically be most effective to pump everything out of the ship, sucking crewmates through the pump like that alien baby thing through the depressurized hole in the wall in Alien 4, you happen to also be a crewmember. So you make sure to use a hose that only pumps water and nothing else. 

Cells use similar pumps embedded in their membranes made out of protein. They use energy to pump things, often very selectively, in or out of the cell. This could be water, ions, or even specific chemicals. 

Well, there is a class of molecular pumps called ATP-Binding Cassette Transporter (ABC Transporter) which specializes in pumping toxins out of cells. Unfortunately, the toxins include many of our cancer drugs. 

Cancer stem cells tend to use ABCs quite a bit and quite often. So the only way to combat this, other than developing new drugs that specifically target and neutralize ABCs, is by dumping so much of the drug into the body that the cancer cells fill up with them faster than they can pump them out. Since cancer cells are highly mutagenic and could potentially just evolve to increase the amount of ABCs, this also must be done so rapidly that the cancer cells don’t have time to adapt. That’s often not an option given how debilitating the side effects can be even in relatively low doses.

The Cancerous Will to Live

There are about a dozen known other mechanisms that CSCs are known to use, but they’re all a lot more technical and mostly revolve around pathways. I strongly dislike pathways as they are extremely complicated and have difficult to remember names. 

Basically, cells have hundreds to thousands of crazy Rube Goldberg machines inside them which control everything. This includes things like apoptosis, which is a mechanism that detects if the cell is mutated or infected then forces the cell to commit seppuku for dishonoring its family. Most cells use this mechanism at several checkpoints during cellular division. 

I say “most” because even healthy, noncancerous stem cells can bypass these checkpoints and divide anyway. The checkpoints do slow things down a lot, and stem cells do need to divide pretty quickly, so I guess that makes sense. Apparently, even nature has to deal with bureaucracy.

Unfortunately, this means that cancer stem cells are also able to bypass apoptosis. A lot of our cancer treatments rely on forcing apoptosis in cancer cells, which often doesn’t affect cancer stem cells since they don’t do that.

Conclusion

Despite the title, I don’t mean to be a huge doomer or say we’ll never cure cancer or anything. That title was just part of my nefarious plot to draw you into my trap using clickbait. Cancer stem cells are just another roadblock we will need to overcome.

Sources:

Fábián, Á., Barok, M., Vereb, G. and Szöllősi, J. (2009), Die hard: Are cancer stem cells the Bruce Willises of tumor biology?. Cytometry, 75A: 67-74. https://doi.org/10.1002/cyto.a.20690 

Pang, L.Y., Argyle, D.J., 2009. Using naturally occurring tumours in dogs and cats tostudy telomerase and cancer stem cell biology. Biochimica et Biophysica Acta1792, 380–391.

Pang L, Bergkvist G, Cervantes-Arias A, Yool D, Muirhead R, Argyle D. Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition, The Veterinary Journal (2012), ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2012.01.009. 

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