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Mechanistic ODE modelling of ovarian tumour microenvironment dynamics under hesperidin exposure

Year: 2026
Type: article
Abstract: Ovarian cancer progression is driven by complex interactions among tumour, immune, stromal, metabolic and angiogenic processes. Although hesperidin exhibits anti-cancer and immunomodulatory activities, its integrated effects on the tumour microenvironment (TME) remain insufficiently understood. This study presents a mechanistic ODE-based framework integrating tumour growth, immune regulation, macrophage polarization, cancer-associated fibroblast (CAF)-mediated extracellular matrix (ECM) remodelling, hypoxia-inducible factor (HIF)−1α/ vascular endothelial growth factor (VEGF)-dependent angiogenesis, glucose–lactate metabolism and redox signalling within a hypothetical ovarian TME centred on PA-1 cells. Simulations across multiple hesperidin concentrations predicted dose-dependent suppression of tumour growth, reduced HIF−1α accumulation, angiogenesis, ECM stiffening and lactate production, accompanied by enhanced anti-tumour immune activity. Local one-at-a-time (OAT) and global Sobol’ sensitivity analyses identified tumour growth kinetics, CAF–ECM interactions, metabolic regulation and selected hesperidin-response parameters as principal determinants of system behaviour. Although not calibrated for quantitative prediction, the proposed framework provides mechanistic insight into how hesperidin-mediated perturbations propagate through interconnected tumour–immune–stromal networks. The model should be regarded as an exploratory, hypothesis-generating platform supporting future experimental validation of hesperidin-mediated mechanisms in ovarian cancer.
DOI: 10.1098/rsos.260368
Institution: Akademia Śląska
Language: English
Open Access status: gold
Estimated APC paid: $1,471
OpenAlex ID: W7106262871
FWCI:
Cites: 109
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Related to: 10