Cancer: looking for simplicity and finding complexity

Abstract

Cancer is one of the most complex dynamic human disease. Despite rapid advances in the fields of molecular and cell biology, it is still widely debated as to how neoplastic cells progress through carcinogenesis and acquire their metastatic ability. The need to find a new way of observing anatomical entities and their underlying processes, and measuring the changes they undergo, prompted us to investigate the Theory of Complexity, and to apply its principles to human cancer. Viewing a neoplasm as a system that is complex in time and space it is likely to reveal more about its behavioral characteristics, and this manner of thinking may help to clarify concepts, interpret experimental data, indicate specific experiments and categorize the rich body of knowledge on the basis of the similarities and/or shared behaviors of very different tumors.

Figure 1

Human beings are complex hierarchical systems consisting of a number of hierarchical levels of anatomical organization (genes, sub-cellular entities, cells, tissues, organs, apparatuses, and organism) that interrelate differently with each other to form networks of growing complexity. Each anatomical entity is embedded in a macro-environmental system that influences the general behaviour of the entity itself.

Figure 2

Multi-state carcinogenesis: a) the schema shows the progression of different qualitative states (x₁, x₂....x_n-1, x_n) identifiable in the development of cancer from normal tissue. The time parameter (t₀, t₁... ....t_n-1, t_n) depends on a large number of variables interconnected in many ways in a non-linear manner. This makes it extremely difficult to predict the exact time interval between two successive states. Although carcinogenesis is a continuum, its differentiation into successive states is still based on differences in histological and clinical data. Examples of dynamical view of colorectal (b) pancreatic (c) and liver (d) carcinogenesis [38,50,51].

Figure 3

Hierarchical manifestation of human cancer. Neoplasia is a complex system determined by a number of processes acting at different molecular and cellular scales, by controls operating over much broader scales, and by factors such as structural controls that may operate at scales ranging from molecular to environmental. The schema exemplify some of the manifestations that can be found at different level of cancer complexity, all of them acting and governed by specific laws that only operate at a particular level.