Modeling intratumor heterogeneity in breast cancer

Reduced therapy response in breast cancer has been correlated with heterogeneity in biomarker composition, expression level, and spatial distribution of cancer cells within a patient tumor. Thus, there is a need for models to replicate cell-cell, cell-stromal, and cell-microenvironment interactions during cancer progression. Traditional two-dimensional (2D) cell culture models are convenient but cannot adequately represent tumor microenvironment histological organization,in vivo3D spatial/cellular context, and physiological relevance. Recently, three-dimensional (3D)in vitrotumor models have been shown to provide an improved platform for incorporating compositional and spatial heterogeneity and to better mimic the biological characteristics of patient tumors to assess drug response. Advances in 3D bioprinting have allowed the creation of more complex models with improved physiologic representation while controlling for reproducibility and accuracy. This review aims to summarize the advantages and challenges of current 3Din vitromodels for evaluating therapy response in breast cancer, with a particular emphasis on 3D bioprinting, and addresses several key issues for future model development as well as their application to other cancers.