Mechanistic ODE modelling of ovarian tumour microenvironment dynamics under hesperidin exposure
- 1Department of Clinical Engineering, Academy of Silesia , Katowice, Poland
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.
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BibTeX
@article{dzik2026mechanistic,
title = {{Mechanistic ODE modelling of ovarian tumour microenvironment dynamics under hesperidin exposure}},
author = {Radosław Dzik},
journal = {Royal Society Open Science},
year = {2026},
month = oct,
doi = {10.1098/rsos.260368},
url = {https://royalsocietypublishing.org/rsos/article/13/10/260368/483916/Mechanistic-ODE-modelling-of-ovarian-tumour},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanistic ODE modelling of ovarian tumour microenvironment dynamics under hesperidin exposure
AU - Radosław Dzik
PY - 2026
DA - 2026/10/07
JO - Royal Society Open Science
DO - 10.1098/rsos.260368
UR - https://royalsocietypublishing.org/rsos/article/13/10/260368/483916/Mechanistic-ODE-modelling-of-ovarian-tumour
AB - 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.
SN - 2054-5703
ER -