What Even is Cancer, Really?

One evening last week, I was rather mindlessly scrolling through my Facebook newsfeed. It was late enough at night that I didn’t want to start anything productive, but not quite late enough to head to bed. Thus, scroll, scroll, scroll, ooohlike, scroll, scroll, hahahawow, scroll, scroll…wait…what?

I had stumbled upon the comments section (dear heavens, save us all) from a crowd-sourcing page for a woman fighting cancer. The woman’s story was heart-wrenching, but the discussion attached the fundraising for treatment had shifted to the efficacy of naturopathic/homeopathic remedies for cancer. I have plenty of thoughts on that subject, but what was clear from my accidental stalking was that the primary arguers (on either side of the camp for/against scientific medicine over “natural remedies”) were a bit murky on what cancer actually is. They both were describing cancer as though it was a condition or infectious disease—perhaps not contagious, but something that can be fought off like a cold or a flu or something like a broken bone that just needs to be properly set to then heal itself.

On the subject of alternative treatments, I refrained from unleashing my two highly opinionated cents; but reading through that comments section reminded me how my own memory was going fuzzy on what cancer really is and what makes it so dangerous. It inspired me to go back to a review paper I haven’t touched in probably five years. Titled “Hallmarks of Cancer: The Next Generation,” the paper succinctly describes the six main trademarks that make a cancer a cancer. Since I was reviewing the paper on my own, I figured I would share the process with all of you. After all, how many of us have been affected by cancer? How many of us have lost loved ones or even suffered from it? Such a ubiquitous issue, we might as well all know a bit more about we’re dealing with.

So what traits make a cancer a cancer? Let’s take a step back. Picture a cell…just any general eukaryotic cell. There is a nucleus to hold the organism’s DNA, organelles to manages essential tasks, and chemical signals floating all about delivering messages to various parts of the cell. Not to mention, outside the cell is a whole world filled with potential chemical signals for daily functioning, and within that cell nucleus are the proper mechanisms to keep the organism’s DNA intact, able to replicate, or ready for a given gene to be expressed once signaled. It’s a complicated world to be “simple.”

eukaryotic cell

Wikimedia commons


Now let’s put together a boatload of different cell types to comprise one single large organism—a human. We are made of varying types of cells that make up tissues, and those tissues make up organs, those organs make up systems, and those systems make up each one of us.

cell tissue organ system


Think of as many different systems and organs as you can. Now think of how many different cell types must be behind each organ or system. We have a lot of diversity that all started with an egg and a sperm! And all of that diversity has led to highly specialized cell types that are responsive to specific chemical signals for proper function, interact in highly specific ways with their neighboring cells, and perform very specific tasks.

Until “normal” cells begin demonstrating cancer behavior, that is. Each of the below traits are present and define what it means to be cancer, no matter the cell type.

Note: all of the information below comes directly from this article . It is a tough review paper to make it through, so this blog post is purely about summarizing the words of the authors. I claim no intellectual property on the cancer information contained in this bad boy!

~The Hallmarks of Cancer~

Sustaining Proliferative Signaling—Imagine this step as someone left the cell division switch in the “constantly on” position. A classic sign of cancer is that you have a group of cells that multiply outside of the normal pattern of cell division. This unregulated growth is called proliferation. Normal cell division is heavily regulated by various molecular “checkpoints,” chemical signals that let a cell know when it needs to divide again. This prevents cells from simply dividing uncontrollably, creating unneeded new cells and wasting energy. Cancer cells, however, have a variety of ways to override normal cell signaling. They can produce their own growth factors (chemical signals for cell division), increase the number of cell-surface protein receptors (allowing themselves to detect any signal that calls for growth), or leave cell division signaling pathways constantly activated. Cancer cells have various ways of making these things happen, but whatever the mechanism, cancer cells are be able to divide uncontrollably.


Normal cell cycle. Source: Penn State University

Evading Growth Suppressors—In the last step, we said that someone left the “on” switch up for cell division, now we are flipping the table altogether. Our bodies also naturally have checkpoints to specifically tell a cell when not to divide. Subtle but important difference. In the last point, cells were trying to constantly find a way to keep the cell division button “on.” Now, our bodies naturally have ways to specifically stop cell division, not just hope the cell doesn’t run into the signal to divide. The problem is, cancer cells can evade the signal that says “stop dividing.” Tumor suppressor genes produce signals that ultimately tell cells to stop dividing. In many cancers, these tumor suppressor signaling pathways are defective. Another little trick cancer cells work around is contact inhibition. In many cell types, just being surrounded by your fellow cells is enough to suppress further cell division. This prevention is called contact inhibition, but some cancer cells are able to evade this inhibition because of faulty cell-surface adhesion proteins. Normal cells can hold together with little locking molecular structures called cadherins, but the cancers who evade suppression in this route have faulty molecular structuring related to this mechanism. Worse, some cancers flat-out hijack normal tumor suppressors (e.g., TGF-beta) and redirects the pathway, which allows for tumor malignancy.

Activating Invasion and Metastasis—This last word is the one we never want to hear because, in a way, we know exactly what it means, but in a way, we still don’t understand it. We know that metastasis means the cancer has spread, but it seems strange how that happened. The primary mechanism is something we just learned about above—cell to cell adhesion molecules. For many cancers, metastasized cells have lost E-cadherin, an important “lock” for cells to stay in place. This allows the broken off cancer cells to travel in various vessels throughout the body. Meanwhile, cadherins that normal promote needed cell migrations are often upregulated to limit normal cell movement.


Metastasis. Source: John Hopkins University

Resisting Cell Death—I think we all remember apoptosis from biology class because it’s just such an odd concept. Programmed cell death? What good is that? It’s actually quite beneficial for ridding the body of stressed or unhealthy to be replaced with new ones, and though it doesn’t happen everywhere in the body all the time, the areas where it regularly occurs (e.g., bone) ensures we have the healthiest tissue possible for high-stress functions. However, apoptosis is a complicated process involving a number of molecular signaling pathways, both direct and indirect. It’s not a simple on/off switch, but cancers have indeed largely lost the response to the signal for apoptosis. There are a number of different places in pathways to make this happen, but unless you like reading strings of letters (I mean it: Bcl-2, Bcl-w, BH3, Bax, Bak, TP53, etc), I’m not going to mention the hotspot proteins and pathways. If you’re interested, flip to page 649 here. Just know that in cancer, the cell signaling pathways for apoptosis are disrupted.


Apoptosis. Source: Duke University

Enabling Replicative Immortality—This one is weird…really weird. Most normal cells can only undergo cell division so many times because they run into a little problem: telomere shortening. Telomeres are little “caps” at the end of every chromosome, but they don’t contain any genes or coded regions. This is important because every time a cell divides, the telomeres are shortened just a little bit during the DNA replication process. The fact that telomeres exist protects our coded DNA, but it does set a finite number of times that DNA can be replicated before we run out of that noncoding buffer zone. This is where cancer is different. In a very small handful of normal cells, there is an enzyme called telomerase. This enzyme adds noncoding DNA back to the ends of telomeres to extend the number of times a cell can divide. Most cancer cells have capitalized on this. Since cancer cells are missing the cue to stop dividing while constantly reacting to the cue to continue dividing, the presence of this enzyme is what allows continued cancer growth. (As an odd aside, telomerase activity is the subject of another focus outside of cancer: treatment for children with progeria.)


Telomeres in green. Source: Stanford University.

Inducing Angiogenesis—All of our tissues need some sort of nutrient supply, and cancer is no different. Early on as cancer cells become a mass, the main concern for the cells is an adequate supply of blood to provide nutrients. Angiogenesis is the main answer. This is the process of signaling blood vessels to produce capillaries and other vessels to supply resources to the growing mass. There are a number of signaling proteins responsible for either activating or opposing angiogenesis, but cancer cells are able to, again, disrupt the appropriate pathways and allow production of blood vessels. What this means is that cancer cells are ultimately able to signal for the production of other cell types (any cell involved in vascularization.) Awareness of this step, though, has opened up a new field for potential cancer treatments.


Tumor inducing angiogenesis. Source: Folkman 2007.

Put these six “hallmarks” all together, and now we have a better understanding of what cancer really is.

paper image

The lingering question we all have, of course, is where does cancer come from? This isn’t discussed in the paper, but when you hear people say “this causes cancer” or “that causes cancer,” what you’re talking about is what gives that first insult to your DNA that allows one of these subtle cell changes to occur. Insults can occur decades apart; and they can come from something we breathe in on a regular basis (cigarette smoke), are exposed to (certain viruses or too much direct UV radiation) or a host of other carcinogens that exist naturally or as a byproduct of our industrial world. Honestly, I would guess that all of us have cells in our body right now that exhibit at least one of these above traits. As we get older, it’s more likely that we have been around long enough that one group of cells will eventually have collected all the ugly Pokemon and wreak havoc on someone’s life.

Another important thing to remember is that cancer cell are someone’s own body cells. Yes, their function has been highly altered, but one of the reasons cancer is so difficult to treat is that a drug must be targeted to only hurt cancer cells, not the rest of the cells in the body. That is very difficult! A few of my friends from grad school went on to the world of cancer research, and they have a tough job! All the respect in the world to them.

I should also point out that I am simplifying the process a bit, but that’s the first step in understanding a complex subject. Do I completely understand cancer myself? Hex to the no I don’t. But I don’t think that’s any reason for us to avoid the subject all together. Exploring the concept can help us make more informed choices or provide a springboard for more learning. I do highly encourage everyone to not just take my word for it, but do your own research—with the caveat that you only trust valid sources! If it’s a blog that starts with “The Truth About Cancer That {insert doctor/pharma/your mom} Doesn’t Want You to Know,” do.not.trust.it.

Well, that’s all for today, but keep exploring!



Cell Division—When a cell divides to create a new genetically identical cell. Remember all that cell cycle jazz? G1 phase (first gap time), S phase (DNA replication), G2 phase (second gap time), and finally M phase (cell division)? Here’s some fun on meiosis and mitosis if you’re interested in a refresher.

Cell signal—any molecule that carries a “message” within or between cells. The message usually induces a reaction of some sort or signals for a cell to perform some activity.

Pathway—Cell signals rarely involve a single chemical. Normally, there is an entire pathway to pass on a message to a cell or the cell neighbor. This is called a signaling pathway. In general, one protein/molecule interacts with another protein/molecule which somehow stimulates a change or activation in that second protein/molecule which then allows it to interact with a third protein/molecule which somehow stimulates a change or activation in that third protein/molecule…bored yet? Yeah, me too, but it that’s how complicated this concept is.

basic signal pathway

Wikimedia commons


insulin pathway.jpg

Hahahaha nope.

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