Where does cancer come from, and why has it not disappeared with evolution? AND Why does vulnerability to cancer persist in most multicellular organisms?
We must look at cancer from a new perspective, taking an evolutionary view. In other words, we must look at cancer through the eyes of Charles Darwin, the father of the theory of evolution.
For a few years now, the joint effort of evolutionary biologists and oncologists has been fostering reflections that translate into transversal advances that are beneficial for both disciplines while changing our understanding.
How the evolution of multicellular organisms sets the stage for cancer
Cancer affects the entire multicellular animal kingdom. It is an ancestral disease related to the appearance of metazoans (animals made up of several cells, as opposed to protozoans made up of a single cell) more than half a billion years ago.
Cancer affects the entire multicellular animal kingdom.
Indeed, this cooperation is sustained by complementary and altruistic behaviours, in particular by apoptosis or cell suicide (by which a cell activates its self-destruction upon receiving a specific signal) and by the renunciation of direct reproduction by any cell that not be a sex cell.
Consequences: resources are depleted, and these cells can then initiate individual or collective behaviours of dispersion and colonisation towards new organs, the sadly known metastases responsible for most deaths due to cancer.
In this way, in a few months or years, a single cancer cell can generate a complex and structured “ecosystem”, the solid tumour (comparable to a functional organ), and metastases more or less disseminated throughout the body.
Persistence of cancer over evolutionary time
From an evolutionary point of view, two hypotheses can explain cancer’s appearance and attributes.
The atavism theory explains cancer as a return to previous cell capacities, among which is the release of an excellently conserved survival program, always present in all eukaryotic cells and, therefore, in all multicellular organisms.
Furthermore, this hypothesis could also explain why cancer cells adapt so well to acidic and oxygen-poor (anoxic) environments since these conditions were common in the Precambrian.
The second hypothesis implies a process of somatic selection -somatic cells group all the cells of an organism except sexual cells- that lead to convergent evolution, that is, to the appearance of similar traits.
This hypothesis suggests that the appearance of the cellular features that characterise “trickster” cells is subject to strong selection each time a new tumour appears, regardless of the immediate causes of these features. Let’s not forget that we only see the cancers that manage to develop, but we don’t know how many “candidates” fail by failing to acquire the necessary adaptations at the right time.
There are different hypotheses about the evolution of cancer.
These two hypotheses are not mutually exclusive: the reappearance of an ancestral program may be followed by somatic selection culminating in convergent evolution. Large animals don’t get cancer anymore.
In natural animal populations, the frequency of cancer varies, in general, between 0% and 40% for all species studied, and there is no relationship with body mass.
This phenomenon is known as “Peto’s paradox”.
The explanation for this paradox is that evolutionary forces have selected more effective defence mechanisms in large animals than in small ones, which makes it possible to reduce the burden linked to cancer due to the increase in size.
A disease that manifests late
Let us also remember that the effectiveness of defences against cancer decreases once organisms have carried out the essentials of their reproduction since evolutionary pressures are less at this stage of life.
The effectiveness of defences against cancer decreases with age.
Our defences against diseases, including cancer, are not outside this operating rule.
Although most cancer mutations occur in somatic cells throughout life, there are rare cases of cancer caused by inherited mutations in the germ line, which produces sex cells.
These genetic mutations are sometimes more frequent than expected from the mutation-selection balance.
Various evolutionary processes can explain this paradox. For example, it has been suggested that natural selection is unlikely to act on such mutations if their adverse health effects only become apparent when the reproductive period is over.
If the initial positive effect is strong, selection may retain that genetic variant even though it causes fatal disease later.
For example, women with a mutation in the BRCA1 and BRCA2 genes have a significantly increased risk of developing breast or ovarian cancer. Still, these mutations appear to be associated with increased fertility.