A critical appraisal of the relative contribution of tissue architecture, genetics, epigenetics and cell metabolism to carcinogenesis

• Published in: Progress in biophysics and molecular biology Vol. 182; pp. 26 - 33
• Main Authors: Grunt, Thomas W., Heller, Gerwin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: Cancer metabolism; Carcinogenesis - genetics; Entropy; Epigenesis, Genetic; Epigenetics; Humans; Mutation; Neoplasms - pathology; Quantum effects; Self-organized criticality; Somatic mutation theory; Tissue organization field theory; Tissue organization field theory; Quantum effects; Cancer metabolism; Epigenetics; Somatic mutation theory; Self-organized criticality; Entropy; Mutation
• ISSN: 0079-6107; 1873-1732; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2023.05.004

Here we contrast several carcinogenesis models. The somatic-mutation-theory posits mutations as main causes of malignancy. However, inconsistencies led to alternative explanations. For example, the tissue-organization-field-theory considers disrupted tissue-architecture as main cause. Both models can be reconciled using systems-biology-approaches, according to which tumors hover in states of self-organized criticality between order and chaos, are emergent results of multiple deviations and are subject to general laws of nature: inevitable variation(mutation) explainable by increased entropy(second-law-of-thermodynamics) or indeterminate decoherence upon measurement of superposed quantum systems(quantum mechanics), followed by Darwinian-selection. Genomic expression is regulated by epigenetics. Both systems cooperate. So cancer is neither just a mutational nor an epigenetic problem. Rather, epigenetics links environmental cues to endogenous genetics engendering a regulatory machinery that encompasses specific cancer-metabolic-networks. Interestingly, mutations occur at all levels of this machinery (oncogenes/tumor-suppressors, epigenetic-modifiers, structure-genes, metabolic-genes). Therefore, in most cases, DNA mutations may be the initial and crucial cancer-promoting triggers.