*Result*: Integrating simulation and experimental validation of nutrient-limited growth in breast cancer spheroids.

*Multicellular tumor spheroids (MCTS) represent a relevant in vitro model for breast cancer (BC), so they are widely used to study cancer pathobiology and evaluate novel antitumor drugs. However, predictive computational tools that simulate these in silico models remain limited, hindering the potential for developing patient-specific therapies. In this work, a COMSOL-based multiphysics model of HER2-positive BT-474 MCTS was developed, integrating Gompertzian growth dynamics, nutrient diffusion, uptake kinetics, and porosity evolution. The model also incorporated an expanding mesh to accurately predict diffusion phenomena. Experimental data on spheroid size, necrotic core formation, glucose consumption, and porosity were used for parameterization and validation. The developed model successfully reproduced growth dynamics, glucose uptake, and necrotic core development. Moreover, a glucose concentration threshold of ∼0.08 mM was identified as critical for necrosis. Oxygen gradients were also simulated, but prediction showed that necrotic levels were not reached. This experimentally based computational model provides a robust platform for investigating tumor behavior under nutrient-limited conditions and may offer a valuable tool for preclinical drug evaluation.
(Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)*