ArticleBioengineering (Basel, Switzerland)2026
A Mathematical Model of Cysteine-Driven Metabolic Adaptation to Hypoxia in Ovarian Cancer.
Article in Bioengineering (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Ovarian cancer progression is strongly influenced by tumour hypoxia and associated oxidative stress. Experimental evidence indicates that cysteine availability supports ovarian cancer cell fitness under hypoxic conditions, yet the quantitative integration of cysteine metabolism, redox control, and energetic maintenance remains incompletely understood. We present a reduced mechanistic mathematical model describing intracellular cysteine allocation between glutathione (GSH) synthesis and hydrogen sulfide production under experimentally imposed hypoxia. The model integrates extracellular cysteine uptake, GSH-dependent reactive oxygen species (ROS) detoxification, hypoxia-amplified ROS generation, and redox-modulated ATP maintenance. Parameter estimation was performed using experimentally derived extracellular metabolite fluxes measured over a 24 h interval. Uncertainty was assessed via bootstrap resampling, and variance-based sensitivity analysis was conducted within (patho)physiologically constrained parameter domains. The calibrated model reproduces extracellular fluxes with relative deviations below 7% and identifies GSH synthesis capacity as the dominant determinant of ATP maintenance within experimentally supported ranges. Hydrogen sulfide (H
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