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 — The Root Cause of Prostate Cancer: A New Understanding of How Progenitor Cells and Microenvironment Degradation Lead to Cancer (Olsen & Liisberg, 2025) — presents the complementary systemic framework that replaces SMT with a model of impaired progenitor differentiation within a degraded connective-tissue microenvironment.
Together, the two papers outline a paradigm shift from mutation accumulation to communication failure as the root cause of cancer.
A layman’s summary of this article is available as supplementary material for non-specialist readers.
