How does age affect cancer progression?

Mónica Vara Pérez · 25-05-2021 10:00 · CEBE answers

Cancer. What a small and scary word, right? Unfortunately, we all have someone in our close circle that has suffered or suffers from this horrible disease. But if we get the question “what is cancer?” or “define cancer in a few words”, most of us go blank. Because we know it is more complex than it seems, but we don’t know where to start. So, before diving into the relationship between age and cancer, let’s briefly go back to what cancer is.

What is cancer?

According to the National Cancer Institute in the US, cancer is “a disease in which some of the body’s (abnormal) cells grow uncontrollably and spread to other parts of the body”. And, as you already know, these abnormal cells are grouped in structures called tumors.

When we talk about a tumor, we imagine it as a clump of cancer cells. However, a tumor is much more than cancer cells. We can actually compare the structure of the tumor with that one of a house: it is mainly formed by bricks (cancer cells), the bricks are put together with cement (extracellular matrix), the house also requires electricity and pipes (blood and lymph vessels) and there needs to be some surveillance and maintenance (immune system). And the stability of the house will also depend on the terrain where it was built (normal tissue).

There are many different cell types in our body, so when each of these cell types becomes abnormal (we can even call it “evil”) and transforms into a cancer cell, will result in a particular type of cancer. For example, in the skin, we can find (among other cell types) melanocytes (the cells that produce melanin, the brown pigment on the skin) and keratinocytes (the cells that produce keratin and contribute to the skin's barrier function) and when they become abnormal, they give rise to very different types of skin cancer: melanoma or keratinocytic carcinoma, respectively.

How do these normal cells become abnormal?

This process of transformation of normal cells into cancer cells is very similar to the process by which a regular person becomes the evil mastermind that wants to bring the world to an end in any action of science fiction movie. Alike these villains, our cells do not become evil from one day to another. Rather, it is a long and sequential process in which a series of unfortunate events (such as mutations), one hit at a time, enables the cells to acquire extra abilities ("superpowers") that eventually allow them to divide and reproduce without control: at this point, they have become cancer cells.

Cancer cells acquire many "superpowers" throughout their life. A very common "superpower" is immortality, or the ability to avoid control mechanisms that our cells or body have in place to prevent this transformation. These control mechanisms ensure that the cell works how it should be and, if it does not (as it would be the case when they suffer a catastrophic event, for example, a mutation that changes the activity of a protein), they will either try to repair the cell to bring it back to its initial state or, if they cannot, they will kill the cell. In fact, most of the normal cells that start this “evil” transformation process will automatically die without getting a chance to complain, and only a very small number of cells will continue the transformation and will end up becoming cancer cells.

Another ‘superpower’ that cancer cells master is the art of camouflage and manipulation. Cancer cells can behave like Agent Smith from The Matrix and this skill is particularly useful within a tumor. For example, the cancer cells will disguise as normal cells so that the surveillance and maintenance crew (the immune system) cannot recognize them and therefore kill them. If the cancer cells are hungry, they will convince the surrounding normal cells to deliver nutrients to them. Or they will make sure that there are additional pipes (blood vessels) built around them so that they do not lack anything.

Unlike in superhero movies (where the same catastrophic event (like a meteorite crash) resulted in people with different superpowers), our cancer cells acquire similar ‘superpowers’ following different catastrophic events (in this example, mutations). This is the reason why different mutations in different proteins give the same "superpower" within the same type of cancer. These different paths help to classify cancer cells from the same type in several subtypes and exploit these differences therapeutically by creating, for each path, custom-made kryptonite. Unfortunately, cancer cells can adapt very quickly and use an alternative superpower to survive, thus making the custom-made kryptonite useless. When this happens, it is called “therapy resistance”.

This is all very interesting… but what does age have to do with any of this?

In the same way that, after a couple of years, our mobile phones or computers start working slower, the battery runs out faster… With the pass of the years, our body also starts losing some abilities: the immune system is less efficient, some cells begin malfunctioning (for example, they divide less frequently, they make more mistakes or start accumulating waste substances, among many other effects), the body becomes a bit weaker and may change the way it retains nutrients, etc. This means that our body will be a bit less able to fight against the transformation of normal cells, and the chances of our cells acquiring abnormal ‘superpowers’ will increase. This is why being over 50 years of age is considered a risk factor for developing cancer. On the other hand, anticancer treatments are generally very aggressive not only for “evil” but for healthy cells too, and aging cells may not tolerate these therapeutics as well as young cells could.

What about younger people?

Cancer in children, adolescents and young adults is not as common as in older people, but some cancer subtypes seem restricted to these age groups. Although it is still not clear which are the factors that drive cancer in early ages (but it is being thoroughly investigated), the subtypes found in young people have been associated with genetic predisposition, meaning that the genetic material of the cells has already partially set them into the path of malignant transformation and that is why (is thought that) they develop cancer at an earlier age. If we look at the scheme above, this genetic predisposition would be the equivalent of starting the process halfway (purple cell). Regarding body fitness and handling therapy, being young can be an advantage in certain cases whereas not make a difference in others.

Unfortunately, for both young and old people, the aggressiveness and outcome of cancer will be mainly dictated by the specific subtype of cancer and the stage in the moment of diagnosis rather than the age of the patient. In short, the earlier it is diagnosed, the better.

During the last decades, enormous research efforts have been (and are being) made to understand and target the versatility and "superpowers" of cancer cells. This resulted in great advancements such as better diagnostic tools or immunotherapy. among many others. We are looking forward to the new options that current cancer research will bring in the future.


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