PERSPECTIVE article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
This article is part of the Research TopicReviews in Gastrointestinal Cancers: Colorectal CancerView all 3 articles
Colorectal Cancer as a Complex Adaptive System: Integrating the Hallmarks of Cancer with Complexity Theory
Provisionally accepted
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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The paradigm of the Hallmarks of Cancer, updated by Douglas Hanahan in 2022, represents one of the most influential syntheses for understanding the functional capabilities that sustain neoplastic transformation. However, its traditional interpretation, often reductionist and fragmentary, does not capture the non-linear, emergent, and adaptive dynamics of tumor behavior. This review proposes a reinterpretation of the hallmarks through the lens of complexity theory, conceptualizing colorectal cancer (CRC) as a self-organizing, open system operating far from equilibrium. Using an integrative conceptual approach, we map the ten classical hallmarks and the new dimensions proposed in 2022 (phenotypic plasticity, non-mutational epigenetic reprogramming, polymorphic microbiomes, and senescence) onto the fundamental properties of complex systems: nonlinearity, emergence, feedback, openness, and historical dependence. We argue that CRC should not be understood as a simple sum of molecular alterations but as a dynamic network of interactions among cells, tissues, and microenvironments where global organization emerges from local rules. This systems-based perspective provides a conceptual foundation for translational models and integrative methodologies in oncology.
Keywords: colorectal cancer, complex systems, emergence, Hallmarks of cancer, self-organization, Systems Biology
Received: 30 Oct 2025; Accepted: 19 Dec 2025.
Copyright: © 2025 Basbus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Luis Roberto Basbus
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