Engineering cancer microenvironments for in vitro 3-D tumor models

TLDR

Tumor microenvironments comprise ECM, vasculature, and stromal cells, yet 2‑D and murine models inadequately recapitulate the 3‑D cell‑cell, cell‑matrix, and heterogeneous signaling needed for drug testing. This review surveys recent advances in 3‑D tumor model generation and outlines future applications for drug testing. The authors compile and analyze scaffold‑based, organoid, and bioprinting strategies used to construct 3‑D tumor models, assessing their relevance to preclinical screening.

Abstract

The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell-cell, cell-matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.