Figure 2.

The tumor microenvironmental factors that cause chemoresistance of cancer cells. Physical cues include the physical barrier, binding to the extracellular matrix component, stiffness-induced mechanotransduction, and fluidic shear stress. Biological and biochemical cues include hypoxia, low pH, cell-cell interaction, cancer-associated fibroblasts, and tumor-associated macrophages. Because each cue induces the chemoresistance of cancer cells through different mechanisms, a combinatorial consideration of those factors using innovative in vitro cancer models is required to identify the exact efficacy of anticancer drugs.