A Critical Re-evaluation of the Somatic Mutation Theory (SMT) Conceptual and Quantitative Limits of the Cell-Centric Paradigm

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.