A Critical Re-evaluation of the Somatic Mutation Theory (SMT) Conceptual and Quantitative Limits of the Cell-Centric Paradigm
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The Somatic Mutation Theory (SMT) frames cancer as a stochastic process driven by the accumulation of random mutations in somatic cells. Using a Poisson–Erlang waiting-time model, we test whether empirical mutation rates and cell-division frequencies permit such multi-hit carcinogenesis within biologically realistic timescales. Even under optimistic assumptions, expected waiting times exceed progenitor-cell lifespans by several orders of magnitude, rendering sequential multi-hit carcinogenesis statistically and biologically implausible. The analysis exposes SMT’s internal inconsistencies and supports a paradigm shift from mutation accumulation to communication breakdown as the root cause of cancer.
Companion Paper Notice
This preprint constitutes Part I of a coordinated two-part series on the origins of cancer.
Part I critically re-examines the Somatic Mutation Theory (SMT), demonstrating its conceptual and quantitative limits as a cell-centric paradigm.
Part II - From Cell-Centric to System-Centric Carcinogenesis: The Repair and Capacity Adaptation (RCA) Conceptual Framework (Olsen & Liisberg, 2025b; Zenodo 10.5281/zenodo.17495975) - presents the complementary systems-biology framework that explains carcinogenesis as failure of progenitor-cell maturation within a degraded connective-tissue microenvironment.
Together, the two papers mark a paradigm shift from mutation accumulation to communication-system failure as the root cause of cancer.
A layman’s summary of Part I is available as supplementary material for non-specialist readers.
