Why Mutation-Centric Models Fail at Late-Stage Cancer

Traditional oncology has long been dominated by mutation-centric paradigms, framing cancer as a cumulative genetic error. However, these models often fail to explain phenotypic convergence and therapeutic resistance in advanced stages. This paper proposes a thermodynamic reinterpretation based on the Theorem of Axiomatic Necessity (TNA), arguing that late-stage cancer is not a product of genetic novelty but a consequence of entropy export failure. By applying the fundamental TNA equation ({d\aleph}{dt} = G - Psi), we demonstrate that once cellular throughput (Psi) collapses, the resulting incoherence accumulation (aleph) forces a regression from specialized functional structures (N^1) to a primitive, high-entropy survival state (N^0). In this framework, late-stage malignancy is viewed as a post-genetic entropic regression where thermodynamic constraints on viability override specific oncogenic drivers. This model shifts the focus from gene-list variation to the mechanical restoration of throughput, offering testable predictions for microenvironmental influence on tumor stability.

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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-01-04
DOI
https://doi.org/10.5281/zenodo.18143077
Primary Topic
Mathematical Biology Tumor Growth
Type
article
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article

Why Mutation-Centric Models Fail at Late-Stage Cancer

Claudio Bresciano
Zenodo (CERN European Organization for Nuclear Research)
Mathematical Biology Tumor Growth
article

Why Mutation-Centric Models Fail at Late-Stage Cancer

Claudio Bresciano
article en

Abstract

Traditional oncology has long been dominated by mutation-centric paradigms, framing cancer as a cumulative genetic error. However, these models often fail to explain phenotypic convergence and therapeutic resistance in advanced stages. This paper proposes a thermodynamic reinterpretation based on the Theorem of Axiomatic Necessity (TNA), arguing that late-stage cancer is not a product of genetic novelty but a consequence of entropy export failure. By applying the fundamental TNA equation ({d\aleph}{dt} = G - Psi), we demonstrate that once cellular throughput (Psi) collapses, the resulting incoherence accumulation (aleph) forces a regression from specialized functional structures (N^1) to a primitive, high-entropy survival state (N^0). In this framework, late-stage malignancy is viewed as a post-genetic entropic regression where thermodynamic constraints on viability override specific oncogenic drivers. This model shifts the focus from gene-list variation to the mechanical restoration of throughput, offering testable predictions for microenvironmental influence on tumor stability.

Zenodo (CERN European Organization for Nuclear Research)
Openalex Percentile: Top 97%
Mathematical Biology Tumor Growth
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Why Mutation-Centric Models Fail at Late-Stage Cancer — Claudio Bresciano · Zenodo (CERN European Organization for Nuclear Research) (2026) | TGRS Research Map | TGRS