Origin of cancer: what is a (cancer) cell? A systems-complexity perspective - principles of cellular systems [part 1]
- 1IB-Cancer Research Foundation, Saarbrücken, Germany
Abstract
In tumor tissue, the same mutations are found as in the surrounding healthy tissue; several pediatric malignancies show few or no mutations; and malignant cells can return to an ordered, non-malignant phenotype when their three-dimensional context is restored. Observations of this kind are difficult to reconcile with the reductionist paradigm that, to this day, regards genetic mutations as the necessary and sufficient condition for the malignant transformation of cells. This paper argues that such an approach does not do justice to the biological reality of the cell as a complex system. As a framework for a systemic alternative, the EMMI variables - Energy (E), Matter/Milieu (M), Mechanics/Structure (M), and Information (I) - are proposed as overarching influencing variables of complex cellular systems and, as the central original contribution of this work, as categorizing hubs that assign the nodes of the cellular network to four classes of physical, chemical or biological influences. Based on the concept of integrative pluralism according to Sandra Mitchell as well as the principles of complexity science, key properties of biological systems - such as emergence, dynamics, nonlinearity, variability, robustness, contingency, and convergence - are presented in terms of their significance for cell biology and carcinogenesis. Furthermore, it is discussed why these are more suitable for explaining the development of cancer in the context of complex cells and cellular systems than a purely mutation-centered approach. The present work is primarily aimed at scientists in the life sciences, such as biologists and physicians, and places particular emphasis on the practical relevance of a systemic approach to the initiation and progression of chronic diseases, particularly malignant tumors. A final chapter is dedicated to integrative pluralism as the epistemological foundation for research into complex systems in biomedicine. The framework thereby becomes operationalizable: the choice of an emergent property defines the explanatory goal, and the selection of the external parameters that stand for the EMMI variables determines what becomes visible and assessable. With a good choice, this selection makes it possible to identify those mechanisms that actually determine the development of disease and cancer, and not merely those that accompany it.
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BibTeX
@article{hanselmann2026origin,
title = {{Origin of cancer: what is a (cancer) cell? A systems-complexity perspective - principles of cellular systems [part 1]}},
author = {Rainer G. Hanselmann},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1936518},
url = {https://doi.org/10.3389/fcell.2026.1936518},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Origin of cancer: what is a (cancer) cell? A systems-complexity perspective - principles of cellular systems [part 1]
AU - Rainer G. Hanselmann
PY - 2026
DA - 2026/10/21
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1936518
UR - https://doi.org/10.3389/fcell.2026.1936518
AB - In tumor tissue, the same mutations are found as in the surrounding healthy tissue; several pediatric malignancies show few or no mutations; and malignant cells can return to an ordered, non-malignant phenotype when their three-dimensional context is restored. Observations of this kind are difficult to reconcile with the reductionist paradigm that, to this day, regards genetic mutations as the necessary and sufficient condition for the malignant transformation of cells. This paper argues that such an approach does not do justice to the biological reality of the cell as a complex system. As a framework for a systemic alternative, the EMMI variables - Energy (E), Matter/Milieu (M), Mechanics/Structure (M), and Information (I) - are proposed as overarching influencing variables of complex cellular systems and, as the central original contribution of this work, as categorizing hubs that assign the nodes of the cellular network to four classes of physical, chemical or biological influences. Based on the concept of integrative pluralism according to Sandra Mitchell as well as the principles of complexity science, key properties of biological systems - such as emergence, dynamics, nonlinearity, variability, robustness, contingency, and convergence - are presented in terms of their significance for cell biology and carcinogenesis. Furthermore, it is discussed why these are more suitable for explaining the development of cancer in the context of complex cells and cellular systems than a purely mutation-centered approach. The present work is primarily aimed at scientists in the life sciences, such as biologists and physicians, and places particular emphasis on the practical relevance of a systemic approach to the initiation and progression of chronic diseases, particularly malignant tumors. A final chapter is dedicated to integrative pluralism as the epistemological foundation for research into complex systems in biomedicine. The framework thereby becomes operationalizable: the choice of an emergent property defines the explanatory goal, and the selection of the external parameters that stand for the EMMI variables determines what becomes visible and assessable. With a good choice, this selection makes it possible to identify those mechanisms that actually determine the development of disease and cancer, and not merely those that accompany it.
SN - 2296-634X
ER -