Survival of the fittest in cancer

One cannot write about evolution without referencing Darwin and his evolutionary theory. It's astounding how relevant this over 150-year idea is. Let's first tease out the theory, so that we are all on the same page.

Darwin described how species evolved via descent with modification. This means that with every generation, there are tiny, unseen changes. Very few modifications, or as we now term them mutations in the DNA will cause a change in the function or phenotype of the organism. However, one day, one organism will be born or acquire a mutation that gives them an advantage over other organisms of the same species. The advantage that it gives the individual means that it is either more likely to survive and/or more likely to offspring and thus pass its genes onto the next generation. This advantageous mutation is therefore being 'selected' to be passed down because the individual that harbours it is fitter than other individuals of the same species. This is the process of natural selection.

For example, the male peacock developed his colourful feathers via mutations in the feather gene that made the colour and shape of the tail more attractive for the female peacock. Male peacocks with this mutation were able to gain a sexual advantage over the male peacocks that didn't the colours, and thus were more likely to mate and produce offspring. The new offspring would be born with the same colourful feathers and hence inherit the advantage with the ladies... This is how all male peacocks eventually all acquired colourful tail feathers.

Likewise in bacteria. The invention of antibiotics revolutionised infection control. However, we are now constantly trying to outsmart the bacteria, which are able develop resistance faster than we can develop drugs. The system works the same way as the peacock. If we expose bacteria to an antibiotic that the bacteria is sensitive to, the bacteria will die. At some point, one single bacteria will be born with or develop a mistake or mutation in its genome that confers resistance to the antibiotic. This means that when you expose the bacteria to the antibiotic, this one bacteria will survive rather than be killed. Because of this, it will live to divide into two daughter cells, and thus pass on the new mutation, or as we call it the newly developed resistance gene to its offspring. They too will be resistant to the antiobiotic. Here we see survival of the fittest, being the bacteria that resisted exposure to the antibiotic, as well as descent with modification as it was able to pass on the new mutation to offspring, creating a new, fitter, evolved version of the species.

The same applies to cancer. It takes a single mutation in crucial cell-cycle control genes for a cell to become cancerous. A cancerous cell is one that has lost control of its cell cycle due. Because of this, cancer cells are genetically unstable - they have also lost the ability to correct mistakes in their DNA, something that healthy cells generally do quite well. What this means is that even though all tumour cells are descendent from the first cancerous cell, there are sub-populations of cancer cells within the one cancer. By the time a cancer is 2mm in size, it may already have a population of cells that are capable of invading the surrounding extracellular matrix and migrating to the bloodstream. These are called Circulating Tumour Cells and may behave differently from the original tumour cells.

Like the bacteria, most of the cancer's cells may be sensitive to the chosen chemotherapy and be killed off. One single cell that is slightly different to the others may be the very cell that is responsible for cancer spread and fatal metastases later on. This cell may have a mutation that, like the bacteria and antibiotics, means that it is resistant to the chosen chemotherapy. Thus, it survives treatment because it is fitter than the rest of the cancer cells, which die. When triggered, it may enter the cell cycle again, leave the blood, enter a new organ and start growing again. We can see the rule of descent with modification is in play here because this new growth will inherit the modified resistance gene. Checking whether the subpopulation of tumour cells responsible for cancer spread is sensitive or resistant to treatment is thus imperative in order to minimise the risk of metastasis.

Next blog: A needle in a haystack: finding Circulating Tumour Cells

More info:

Practitioners: P Goymer, 2008, Natural selection: the evolution of cancer, Nature, (454) 1046 - 1048 - Read the article

Patients: A great video explaining descent with modification and natural selection can be found here