Based at the Moffitt Cancer Center, Florida, Cancer Ecology is a small research group led by David Basanta. We are mathematical modellers who work with biologists and clinicians, trying to understand the ecology of tumors and the evolutionary dynamics of cancer progression and resistance to treatment.

Gatenby and Gillies: a microenvironmental model of carcinogenesis

Giving the finishing touches to a paper which I am writing with people in Dresden and Lyon, I came across an interesting article:

R. Gatenby and R. Gillies. A microenvironmental model of carcinogenesis. Nature Reviews Cancer 8, 56-61 (2008)

Neither Gatenby nor Gillies are mathematicians (the first is a physician whereas the second is a biologist) but both have worked before on some rather interesting models of carcinogenesis. In this paper they again introduced one of their models, constructed around a differential equation with a Lotka-Volterra term, in order to study how the microenvironment contributes to select phenotypical traits (conferred by genetic mutations).

The phenotypical traits are:

  • Insensitivity to anti growth signals.
  • Self sufficiency in growth signals.
  • Limitless replication.
  • Abnormally high glucose uptake
  • Resistance to acid mediated toxicity
  • Invasion and metastases with sustained angiogenesis

This list is very similar to the one proposed by Hanahan and Weinberg (which long time readers of this blog might be familiar with). The biggest difference is the emphasis on acidity and glucose consumption, stuff related with the glycolytic metabolism, whose importance in tumour progression has been championed by Gatenby.

This is very relevant research and the authors do well to point out that most cell-centric models study tumour progression without questioning much why specific phenotypical changes are necessary. The answer is of course in the microenvironment, that allows those phenotypes that are better adapted to survive and grow. Microenvironental features represent barriers that limit tumour growth and thus, the phenotypes that manage to overcome them (whatever the genetic or epigenetic mechanism they exploit) will prosper, probably at the expense of the less adapted phenotypes.

 

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