Chapter 5: Mimicking Chemical Features of the Tumor Microenvironment

The tumor microenvironment (TME) plays a central role in tumor progression and metastasis, thereby regulating disease prognosis and patient outcomes. Systematic investigation of the multitude of factors influencing the solid TME is necessary to understand the mechanisms of disease progression. Particularly, the role of cancer cell–matrix interactions and multi-directional crosstalk between tumor and stromal cells have gained attention as potential therapeutic targets. Toward this end, engineered two-dimensional (2D) and three-dimensional (3D) tumor models have been developed using biomaterial-based platforms for various mechanistic studies as well as translational drug-screening applications. In this chapter, we discuss specific cellular and extra-cellular matrix (ECM) components of the TME that regulate tumorigenic and metastatic progression. We describe in detail a wide range of natural and synthetic biomaterials that have been implemented as in vitro platforms for cancer studies. We specifically discuss various chemical modifications of these materials to tune their biochemical and biophysical properties toward emulating native tumor tissues. We further present novel advances in biomaterial design and user-controlled spatiotemporal regulation of material properties that help mimic the dynamic and heterogenous nature of the TME. Overall, the implementation and translation of these engineered scaffolds and matrices will significantly accelerate the anti-cancer drug discovery efforts in the future.