Hypothesis of Carcinogenesis as Loss of Multicellular Cohesion and Activation of an Ancient Autopoietic Fallback Program

Abstract The somatic mutation theory (SMT), despite decades of dominance in oncology, fails to explain key phenomena: why most individuals exposed to strong carcinogens never develop clinical cancer (14%/86% ratio in smoking and lung cancer), why tumors can remain dormant for years, why identical mutations yield divergent outcomes, and why cancer occurs across phylogenetically distant organisms from Hydra to humans. This paper presents NOAH6, a comprehensive information-theoretic model of carcinogenesis that redefines malignant transformation as a deterministic sequence: chronic stress → loss of multicellular cohesion → decline of the cohesion index below a critical threshold (K < T) → collapse of the lamina-heterochromatin repression complex (Level 4) → derepression of the ancient algorithm (Level 5) → activation of autonomous mode → formation of the first tumor clone. The model distinguishes two phases: Cancerᵢnitiation (local loss of cohesion, universal to all multicellular organisms) and Cancerₛystemic (hijacking of the central regulator R3 and establishment of the permissive state Pₛtate, specific to complex organisms with developed neuroendocrine systems). Testable concepts are introduced: the cohesion index K (t) with memory decay λ, the phase transition threshold T, the five-layer Level 1–5 architecture linking the cell surface to the genome, and hypoxia as the evolutionarily oldest universal signal of endangered multicellularity. NOAH6 is not a discovery of new molecules but a novel architecture for existing phenomena. The model generates seven experimentally falsifiable predictions and offers therapeutic strategies based on informational system reset rather than cytotoxic cell elimination.