CancerEvo is a research group led by David Basanta

We are mathematical modellers who work with biologists and clinicians

We try to understand

  • the ecology of tumors

  • the evolutionary dynamics of cancer progression

  • resistance to treatment

Based at the Moffitt Cancer Center, Florida

The Darwinian perspective, the mutator phenotype and response to stress

Although today I will be writing about a paper recently published in the international journal of Epidemiology and authored by Paolo Vineis and Marianne Berwick, this is not going to be a review in the usual sense. This time I would like to write about the ideas and make no reference to the methodology.

The Vineis and Berwick emphasize the role of population dynamics on cancer progression. The usual view on cancer is that cancer cells grow at a faster rate than normal cells and that is the reason why they end up (if successful) killing the host. Growing populations can be due to this but they can also be the result of other factors (think of longer lifespan). The authors hint that the success of most cancers (with respect to taking over a tissue) lays on the fact that cancer cells have a greater proportion of replicating daughter cells. That makes sense to me. For instance, in a tumour whose cells that are capable of dividing near the tumour growth front (let's call them motile tumour cells) will have an advantage over other non motile but faster proliferating tumour cells in terms of how many of its daughter cells will be in position to proliferative (regardless to the speed at which they can divide).

The authors have also something to say about the highly controversial topic of the mutator phenotype. Quick reminder: the amount of time to pick up all the mutations necessary for a neoplastic cell to become a cancer cell is, according to some researchers, big enough as to be unlikely to happen in our life time. Thus cancer is the consequence of a single mutation that makes the cell more likely to produced mutated offspring. To prove their point they compare tumour cells to the behaviour of E.coli under stress. Under normal circumstances the mutation rate of the E.coli is low but when the going gets tough the mutation rates increases significantly. The speculation is that this is no accident but a feature of the bacterial DNA that in such a way can explore a genetic solution out of the problem. Could tumour cells be attempting something similar?

I find this hypothesis quite interesting and from my limited experience it seems quite novel. It should be interesting to do some experimental work (maybe more than theoretical) to see if there are any molecular mechanisms that might have an effect on the probability of mutation (say, the DNA repair mechanism) that could be held down when there are 'stress' signals in the environment. It could even be that the mechanism is similar to that of the E.coli although since bacteria are far simpler cells than human cells that could be unlikely (not having any experience with molecular biology should make any one be skeptic about statements like this).

Spencer et al: Modeling Somatic Evolution in Tumorigenesis

Edge of existence