Anatomically aware simulation of patient-specific glioblastoma xenografts

TL;DR

A new simulation model for glioblastoma growth in mice uses anatomical brain maps and patient-specific data to improve preclinical research and treatment design.

Contribution

The novel framework uses anatomically aware simulations and Approximate Bayesian Computation to model patient-specific glioblastoma xenografts with high accuracy.

Findings

The model accurately simulates tumor growth patterns observed in mouse xenograft experiments.

Adjusting model parameters allows simulation of treatment effects and improves statistical power in preclinical studies.

The framework supports case-specific comparisons and reduces reliance on animal experiments.

Abstract

Patient-derived cells (PDC) mouse xenografts are increasingly important tools in glioblastoma (GBM) research, essential to investigate case-specific growth patterns and treatment responses. Despite the central role of xenograft models in the field, few good simulation models are available to probe the dynamics of tumor growth and to support therapy design. We therefore propose a new framework for the patient-specific simulation of GBM in the mouse brain. Unlike existing methods, our simulations leverage a high-resolution map of the mouse brain anatomy to yield patient-specific results that are in good agreement with experimental observations. To facilitate the fitting of our model to histological data, we use Approximate Bayesian Computation. Because our model uses few parameters, reflecting growth, invasion and niche dependencies, it is well suited for case comparisons and for probing treatment effects. We demonstrate how our model can be used to simulate different treatment by perturbing the different model parameters. We expect in silico replicates of mouse xenograft tumors can improve the assessment of therapeutic outcomes and boost the statistical power of preclinical GBM studies.

Glioblastoma is the most common and aggressive brain tumor in adults. To aid in research, it is common to use mouse models created by implanting patient-derived tumor cells, which provide a controlled system to study glioblastoma growth and treatment response. While these models are essential for preclinical studies, they are costly, time-consuming, and cannot easily capture the variability observed across patients. In this study, we introduce a simulation model that simulates how patient-derived glioblastoma tumors grow in the mouse brain. Our approach uses detailed maps of brain anatomy and a small number of biologically motivated rules to recreate how tumors expand, invade, and respond to their environment. By adjusting the model to match experimental data, we can reproduce case-specific tumor growth and explore how different treatments might work. This “virtual laboratory” has the potential to reduce reliance on animal experiments, improve the interpretation of preclinical studies, and ultimately support the design of more effective therapies for glioblastoma.

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