Hybrid Cellular Automata Modeling Reveals the Effects of Glucose Gradients on Tumour Spheroid Growth

Simple Summary In recent years, mathematical models have revolutionized cancer research, illuminating the complex dynamics of tumor growth and aiding drug development. These models, reflecting biological and physical processes, are increasingly used in clinical practice, offering precise patient-specific predictions. Our work introduces an innovative in silico model to simulate tumor growth and invasiveness. The automated hybrid cell, replicating key tumor cell features, enables exploration of 3D tumor spheroid evolution. Sensitivity analyses reveal that tumor growth is primarily influenced by cell replication speed and adhesion, while invasiveness relies on chemotaxis. These insights shed light on tumor development mechanisms, guiding effective strategies against tumor progression. Our model serves as a valuable tool for advancing cancer biology research and potential therapeutic interventions.Abstract Purpose: In recent years, mathematical models have become instrumental in cancer research, offering insights into tumor growth dynamics, and guiding the development of pharmacological strategies. These models, encompassing diverse biological and physical processes, are increasingly used in clinical settings, showing remarkable predictive precision for individual patient outcomes and therapeutic responses. Methods: Motivated by these advancements, our study introduces an innovative in silico model for simulating tumor growth and invasiveness. The automated hybrid cell emulates critical tumor cell characteristics, including rapid proliferation, heightened motility, reduced cell adhesion, and increased responsiveness to chemotactic signals. This model explores the potential evolution of 3D tumor spheroids by manipulating biological parameters and microenvironment factors, focusing on nutrient availability. Results: Our comprehensive global and local sensitivity analysis reveals that tumor growth primarily depends on cell duplication speed and cell-to-cell adhesion, rather than external chemical gradients. Conversely, tumor invasiveness is predominantly driven by chemotaxis. These insights illuminate tumor development mechanisms, providing vital guidance for effective strategies against tumor progression. Our proposed model is a valuable tool for advancing cancer biology research and exploring potential therapeutic interventions.