Reconstruction of tumor microenvironment via in vitro three-dimensional models

Abstract Recent advances in tumor microenvironment (TME) modeling as well as its applications to cancer therapy has brought various dramatical changes in multiple malignancies management. Understanding the mechanisms of response and resistance to cancer therapy requires a clear elucidation of the intricate interactions between TME cells, the surrounding stroma, and distant affected tissues or organs. To address this demand, various three-dimensional (3D) cell culture techniques have been developed in order to recapitulate and understand cancer biology over the past decade. This review summarizes some saliant progresses in in vitro 3D TME modeling, including the cell-based, matrix-based, and vessel-based dynamic 3D modeling techniques and their applications in investigating tumor-stroma interactions and responses to cancer therapies. The review also discusses the limitations of current TME modeling approaches and proposes some new thoughts on the construction of more clinically relevant models.