An Emergence Framework of Carcinogenesis.

Elizabeth A W Sigston,Bryan R G Williams

doi:10.3389/fonc.2017.00198

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.

Highlights

Consideration given to paradigms that provide the framework for the understanding of carcinogenesis by physicians, surgeons, in every day practice of managing and treating cancer is minimal
While there are a number of models of carcinogenesis, these have evolved through the interaction of several disciplines and can be grouped into two main theories: those that consider cancer to be a genetic disease, including somatic mutation theory (SMT), multistage models, and evolutionary models that consider the development of cancer to be due to temporal changes related to variation and selection and place genetic modifications with alteration in phenotype as the key driver of carcinogenesis [8,9,10,11], and those that consider cancer to be an issue of tissue organization, such as tissue organization field theory (TOFT) and inflammatory models [11,12,13,14]
This paper presents a comprehensive framework for carcinogenesis

Summary

INTRODUCTION

Consideration given to paradigms that provide the framework for the understanding of carcinogenesis by physicians, surgeons, in every day practice of managing and treating cancer is minimal. The predominant traditional model of cancer, the somatic mutation theory (SMT), in which cancer is considered a genetic disease [3,4,5,6,7], has been widely accepted as factual, rather than theory [1, 4, 5] This narrows avenues of new research and directs the way in which data is analyzed [6]. The central proposition is a change in the way cancer is investigated, managed, and treated, by considering ‘cancer’ as an ‘emergent system’ This clear and well-defined framework allows integration of progress and discoveries made to date regarding carcinogenesis and cancer, and provides alternative ways to view that and new knowledge, driving the progress of research toward making an impact at the place that truly matters, the bedside

Background

CONCLUSION