An Emergence Framework of Carcinogenesis

Abstract

Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT), in which cancer is considered a genetic disease, has been the predominant traditional model of cancer for over 50 years. More recently, alternative theories have been proposed, such as tissue organization field theory (TOFT), evolutionary models, and inflammatory models. Key concepts within the various models have led to them being difficult to reconcile. Progressively, it has been recognized that biological systems cannot be fully explained by the physicochemical properties of their constituent parts. There is an increasing call for a ‘systems’ approach. Incorporating the concepts of ‘emergence’, ‘systems’, ‘thermodynamics’, and ‘chaos’, a single integrated framework for carcinogenesis has been developed, enabling existing theories to become compatible as alternative mechanisms, facilitating the integration of bioinformatics and providing a structure in which translational research can flow from both ‘benchtop to bedside’ and ‘bedside to benchtop’. In this review, a basic understanding of the key concepts of ‘emergence’, ‘systems’, ‘system levels’, ‘complexity’, ‘thermodynamics’, ‘entropy’, ‘chaos’, and ‘fractals’ is provided. Non-linear mathematical equations are included where possible to demonstrate compatibility with bioinformatics. Twelve principles that define the ‘emergence framework of carcinogenesis’ are developed, with principles 1–10 encapsulating the key concepts upon which the framework is built and their application to carcinogenesis. Principle 11 relates the framework to cancer progression. Principle 12 relates to the application of the framework to translational research. The ‘emergence framework of carcinogenesis’ collates current paradigms, concepts, and evidence around carcinogenesis into a single framework that incorporates previously incompatible viewpoints and ideas. Any researcher, scientist, or clinician involved in research, treatment, or prevention of cancer can employ this framework.

Germline variation networks in the PI3K/AKT pathway corresponding to familial high-incidence lung cancer pedigrees

“…For example, alterations in CDK1 and CDK2 enzyme kinetics parameters will disrupt the regular cell cycle [29]; the in vitro tumor cell proliferation dynamics follows a fractal structure different from normal oscillatory dynamics [30]. Although mathematical nonlinear theories are thought to model carcinogenesis in pure theoretical approaches [31], our results may provide explicit and experimental support of this philosophy. This theory may also apply to other types of cancer.…”

Precision medicine in an imprecise and complex world: Magic bullets, hype, and the fuzzy line between health and disease

“…A broader perspective of cancer is needed, a different way of conceptualizing cancer, its development, and its behaviour . Several have taken a complex systems approach . For example, Sigston and Williams proposed a series of 12 somewhat overlapping principles in their Emergence Framework of Carcinogenesis .…”

“…Several have taken a complex systems approach . For example, Sigston and Williams proposed a series of 12 somewhat overlapping principles in their Emergence Framework of Carcinogenesis . Principle 1 states that “cancer is a dynamic complex system emerging at the level of the ‘functional tissue unit.’” Other principles emphasize emergence and equifinality, ie, that common properties of cancer can be accomplished via different systems utilizing different mechanisms, multiscale causality, and dynamics.…”

Perspectives on Complexity, Chaos and Thermodynamics in Environmental Pathology

“…In fact, complexity science and chaos theory have gone far beyond scientific, academic interest, becoming a common scientific divulgation theme. Nevertheless, medical disciplines, and pathology in particular, still rely on a deterministic, reductionistic approach and still hesitate to fully appreciate the intrinsic complexity of living beings, aside from some noticeable exceptions [ 4 , 5 , 6 , 7 , 8 , 9 ].…”