Tumour-on-a-Chip: Perfusion Systems to Model the Extracellular Breast Tumour Microenvironment—From Tumour Progression to Metastasis Formation

The integration of three-dimensional (3D) tumour models in perfusion systems has provided new tools to study cancer and metastasis. Such systems are designed to have a high degree of control over biophysical properties of the extracellular tumour microenvironment (TME), and cellular composition. Advancement in 3D models, tissue engineering, biomaterials and microfluidics has allowed an extra level of control over spatial and temporal properties of the TME, and multiplexed in vitro models helped in enhancing knowledge on tumour development, progression and formation of distal metastasis. Advanced 3D tumour in vitro models are nowadays used not only to understand tumour development but also to provide tools for testing therapies and improve preclinical drug development. Breast cancer is one of the most diagnosed types of cancer, with high incidence of recurrent metastasis to bone. Many in vitro models are designed to mimic breast cancer and metastasis to bone and used in early metastatic detection, drug screening and therapy intervention. In this chapter, physical properties of the breast TME are discussed with specific reference to perfusion and microfluidic systems. Advantages of perfusion systems to control flow rates, shear stresses and transmission of mechanical forces, nutrient and oxygen delivery are presented. Ultimately, breast cancer cells’ extravasation and formation of distal metastasis to bone-like recipient are discussed with critical perspective to current knowledge-gaps.