Novel 3D tumouroid models for precision modelling of cancer cell invasion in vitro

Current 3D models, though valuable, fall short in replicating the complexity of the tumor microenvironment (TME). To overcome these limitations, we propose a multi-faceted model incorporating synthetic ECM analogs with tailored control over stiffness and composition to mimic the native extracellular matrix (ECM).

In addition to introducing key stromal cell types such as fibroblasts, immune cells, and endothelial cells, we will incorporate tumor microenvironment (TME) gradients, simulating variations in oxygen, nutrient levels, and growth factors. This will allow the model to replicate the hypoxic and nutrient-deprived conditions that cancer cells face in vivo.

Simulated vascular networks using microfluidic systems will recreate blood flow, enabling the study of cancer-vasculature interactions in real-time. The model will also feature real-time monitoring of ECM degradation by incorporating sensors or fluorescent markers to study proteolytic activity during invasion.

Furthermore, we will integrate a drug delivery simulation system, allowing us to observe drug diffusion, uptake, and cancer cell responses in a more realistic environment. This feature will help in assessing drug efficacy, resistance, and the role of the TME in drug delivery.

By combining these features, this advanced 3D model will provide a comprehensive and realistic platform for studying cancer cell invasion, improving our understanding of tumor progression and enhancing drug discovery efforts.

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Time lapse video of the tumour spheroid invading the 3D matrix