Cancer initiation and progression: an unsimplifiable complexity

Abstract

Background: Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated.

Conclusion: There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours.

Figure 1

Natural cells and their tumoural counterparts can be viewed as sets of different entities and/or behaviours.

Figure 2

Natural and tumoural cells share a number of properties (green area), and this sharing can be schematized using set theory.

Figure 3

The progressive transformation of natural cells into cancer cells. This schema shows the dichotomous generation of a cancer cell as a distinct entity (a) or with a number of functions shared with a natural cell. The area of the intersection is proportional to the number of shared properties: a zero area indicates that the cancer cell is a wholly distinct entity, whereas its progressive but time-limited reduction leads to a cell that has a proportion of shared behaviours and a proportion of distinct properties that determine its tumoural nature i.e. tumour growth, invasiveness, metastatic potential and responsiveness or resistance to therapy (b).