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Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
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A Structural Argument for Multi-Angle Cancer Intervention: What the mathematics of sequential thresholds predicts about combination therapy -- and where to test it

Authors: van der Klein, Raimo;

A Structural Argument for Multi-Angle Cancer Intervention: What the mathematics of sequential thresholds predicts about combination therapy -- and where to test it

Abstract

The dominant approach in cancer treatment is direct confrontation: identify the tumour, send a drug to fight it. One drug against one target on the battlefield of advanced disease. This paper proposes a structural alternative. If cancer is understood as a dissipative system that runs a cycle -- sixteen steps in a mandatory order, each producing the input for the next -- then every step contains a threshold that must be crossed for the tumour to advance. Each threshold is itself a four-step process. The mathematics of sequential gates shows that attacking a threshold at all four of its sub-steps blocks 99% ofcrossings, while attacking a single sub-step blocks only 70%. Reaching 99% with one drug would require 100-fold potency over the biological process. Reaching 99% with four drugs requires only 3-fold potency each. Four moderate drugs beat one miracle drug. This paper identifies thirty-six intervention points across nine actionable positions in the tumour lifecycle, names the molecular target at each, and maps the existing drug that addresses it. 89% of these drugs are approved or in clinical trials. The proposal is not to fight the tumour head-on with a single weapon, but to place four obstacles at each threshold the tumour must cross -- before it reaches the next stage. Not a battle. A series of barriers that make progression structurally impossible.

Keywords

cancer combination therapy, tumour lifecycle, systems oncology, dissipative systems, cancer, multi-angle intervention

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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Cancer Research
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