A comprehensive review of 3D cancer models for drug screening and translational research

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research.In addition to cancer cells,a range of other factors include the stroma,density and composition of extracellular matrix,cancer-associated immune cells(e.g.,cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions,and a number of other factors(e.g.,tumor vasculature and tumor-like microenvironment in vivo)has been widely ignored in the 2D concept of culture.Despite this knowledge,the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials.This review discusses the immense importance of tumor microenvironment(TME)recapitulation in cancer research,prioritizing the individual roles of TME elements in cancer histopathology.The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement,components,and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials,some of which are discussed here.Furthermore,it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors.Furthermore,this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.