Should we rethink existing types of cancer?

How is it classified in biology and medicine?

One of the greatest attempts at classification in biology was made by Carlos Linnaeus. In the 18th century, this Swedish biologist undertook the monumental project of giving Latin names to the countless living organisms known at the time. Linnaeus assigned each organism a sequence of names, the configuration of which helped group related organisms. For example, the wolf is Canis lupus, and the dog is Canis lupus familiaris.

Linnaeus did such a good job that this classification is still valid today, although many of us do not understand Latin. Although we see that it is not immune to the prevailing fashion, when the discipline needs to give a name to new objects or phenomena.

And how was cancer first classified? The disease has been known since the times of Ancient Egypt, but it experienced its revolution in the first half of the 20th century, when radiation was discovered and proven to help eliminate tumors. At that time, everything in medicine revolved around tissues and organs. It was therefore natural that cancers were named after the tissue or organ in which they arose: pancreatic cancer, lung cancer, etc. And, as with Linnaeus’ classification, this continues to this day.

However, in other, more modern disciplines, such as immunology, a “classifying” moment occurred when biology focused on what happens inside cells rather than on the place they occupy in the body. That is, we were talking about molecules.

In the case of immune cells, molecules on their surface were used that allow them to differentiate cells from others. And since there are a lot of different molecules, immunologists did not complicate their lives and assigned them a code of letters and numbers like “CDx”, where “x” is a number (CD1, CD2, CD3…). Thus, cells are named depending on how many of these molecules they express (+) or do not express (-) on their surface (for example, a cell CD1⁺CD2⁺CD3⁻).

As a result of this type of classification, immunological language was understood only by specialists, and for researchers in other disciplines (not to mention the average citizen) it was difficult. This is precisely what popularizer Philip Dettmer complains about in his recent book Immunity. This highly regarded work explains the functioning of the immune system at an accessible level, but at the same time reflects the layperson’s difficulty in handling immunological terminology.

The molecular stage of cancer begins

Let’s return to the case of cancer. Times change, and what was relevant 50 years ago is not always relevant now. And cancer research has advanced by leaps and bounds in recent decades, so more and more experts say it’s time to rethink the classification of this disease.

This is echoed in a recent commentary published in the journal Nature by a group of French researchers. The authors state that over the years, cancer has been treated (with surgery, radiation, or chemotherapy) depending on the organ in which it originated; that’s where his “taxonomy” comes from. However, with the discovery of the molecular mechanisms that drive the disease, molecular markers have emerged that can become targets for therapy. Moreover, these markers may be common to several types of cancer.

And what problem arises? Well, quite a serious case. Clinical trials are currently based on anatomical classification of cancer. However, it is now being seen that some patients with a certain type of cancer may potentially respond to treatments that have been tested on another type of cancer. The worst part is that they can’t get it until the drug is tested in clinical trials for its specific modality. And because clinical trials tend to take longer, many patients who could be cured die.

For this reason, the authors of a recent article are calling for an urgent change in the classification of cancer so that it is based on molecules rather than organs.

But is there such a rush?

This is not a new discussion. Other researchers have previously highlighted the need to expand the classification of cancer types by integrating new data on new molecular markers.

In fact, in 2018, the journal Cell published the result of an extensive study that combined the anatomical origin of a tumor with molecular markers of its cells, proposing a type of classification that included both aspects. This has resulted in the design of umbrella-type clinical trials, in which different mutations contained in tumor cells are integrated within the same anatomical origin of a tumor in order to refine the type of treatment.

Another reason not to abandon the anatomical component in the classification is that the nature of the disease is closely related to the organ in which it occurs.

Any cancer occurs because a cell that should no longer divide (that is, “differentiate”) begins to multiply uncontrollably. We can think of cell differentiation as a process in which cells progress through stages (from least differentiated to most differentiated). As they progress, they gradually lose the ability to divide and increasingly resemble the cells that make up a mature organ.

Well, in most cases, tumors are formed by already differentiated cells that “regress” in this process and regain the ability to reproduce. This is what is called “dedifferentiation.” But they usually do not return to the “starting box” (that is, to a completely pluripotent cell, like the one that gives rise to a full-fledged organism), but remain halfway. For example, a breast cancer cell is different from a pancreatic cancer cell, although they share molecular markers and could potentially respond to similar treatments.

Because of this inherent difference, they are not guaranteed to respond the same way to treatment. This type of important information would be lost if cancers were classified solely based on molecular criteria.

Moreover, there is the problem of the “opacity” of a discipline when it is classified on the basis of molecules, as we saw with the example of immunology. If such an extreme measure as abandoning anatomical notations in favor of molecular notations is taken, the field of cancer may become incomprehensible to non-specialists. An area where even the patients themselves would not be able to understand what type of cancer they have without taking a course in molecular biology.

It would be a less attractive discipline for researchers from other disciplines and would be difficult to explain to potential investors. All for the sake of speeding up clinical trials? Wouldn’t it be better to make the design of these clinical trials more flexible, allowing the process to be accelerated for one type of cancer when a treatment has already been proven safe for another?

As always, time and debate will answer these questions. But history teaches us that we should not allow ourselves to be carried away by fleeting fads.

This article was published in Conversation magazine.