Microphysiological Systems as Enabling Tools for Modeling Complexity in the Tumor Microenvironment and Accelerating Cancer Drug Development

Abstract Tumor cell heterogeneity with distinct phenotypes, genotypes, and epigenetic states as well as the complex tumor microenvironment is major challenges for cancer diagnosis and treatment. There have been substantial advances in our knowledge of tumor biology and in the capabilities of available biological analysis tools; however, the absence of physiologically relevant in vitro testing platforms limits our ability to gain an in‐depth understanding of the role of the tumor microenvironment in cancer pathology. In this review, recent advances in engineered tumor microenvironments to advance cancer research and drug discovery are presented, including tumor spheroids, microfluidic chips, paper scaffolds, hydrogel‐based engineered tissues, 3D bioprinted scaffolds, and multiscale topography. Furthermore, how these technologies address the specific characteristics of the native tumor microenvironment is described. Through the comparison of these biomimetic 3D tumor models to conventional 2D culture models, the validity and physiological relevance of these platforms for fundamental in vitro studies of the tumor biology, as well as their potential use in drug screening applications, is also discussed.