The Systemic-Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System.

Antonio Mazzocca

doi:10.3390/ijms20194885

Abstract

The Systemic–Evolutionary Theory of Cancer (SETOC) is a recently proposed theory based on two important concepts: (i) Evolution, understood as a process of cooperation and symbiosis (Margulian-like), and (ii) The system, in terms of the integration of the various cellular components, so that the whole is greater than the sum of the parts, as in any complex system. The SETOC posits that cancer is generated by the de-emergence of the “eukaryotic cell system” and by the re-emergence of cellular subsystems such as archaea-like (genetic information) and/or prokaryotic-like (mitochondria) subsystems, featuring uncoordinated behaviors. One of the consequences is a sort of “cellular regression” towards ancestral or atavistic biological functions or behaviors similar to those of protists or unicellular organisms in general. This de-emergence is caused by the progressive breakdown of the endosymbiotic cellular subsystem integration (mainly, information = nucleus and energy = mitochondria) as a consequence of long-term injuries. Known cancer-promoting factors, including inflammation, chronic fibrosis, and chronic degenerative processes, cause prolonged damage that leads to the breakdown or failure of this form of integration/endosymbiosis. In normal cells, the cellular “subsystems” must be fully integrated in order to maintain the differentiated state, and this integration is ensured by a constant energy intake. In contrast, when organ or tissue damage occurs, the constant energy intake declines, leading, over time, to energy shortage, failure of endosymbiosis, and the de-differentiated state observed in dysplasia and cancer.

Highlights

I recently proposed the systemic–evolutionary theory of cancer (SETOC) as a new theory about the origin of cancer [1,2,3]
The SETOC postulates that one of the fundamental processes underlying the origin of cancer is the progressive breakdown or uncoupling of endosymbiosis between two cellular “subsystems”, namely, (i) the mitochondria/cell bioenergetics and (ii) the informational nuclear–cytoplasmic component, which have co-evolved into the eukaryotic cell
The concept of endosymbiosis here mostly refers to the symbiogenesis or endosymbiotic theory according to Lynn Margulis

Summary

Introduction

I recently proposed the systemic–evolutionary theory of cancer (SETOC) as a new theory about the origin of cancer [1,2,3]. Factors causing the breakdown (or the uncoupling) of endosymbiosis include all those factors that induce, over time, persistent alterations of tissues or tissue damage including cyto-architectural degenerations, which activate processes such as chronic inflammation and repair processes as well as fibrogenesis, along with the genetic/epigenetic modifications and vascular/stromal changes observed in cancer. This supports the thatprimordial insults to abehaviors tissue, by affecting its often observed in cancer cells This supports the concept that insults to a tissue, by affecting its architecture, can cause the uncoupling of cellular endosymbiosis. The SETOC posits that the de-emergence of the “eukaryotic cell system” and re-emergence of the archaea-like and prokaryotic-like subsystems, featuring uncoordinated behaviors leading to cellular transformation, result in a sort of “cellular regression” towards ancestral or atavistic biological functions and behaviors (similar to those of protists or unicellular organisms in general).

Further Explanations

Conclusive Remarks