Compared with traditional 2D cultivation models, 3D sphere models can better simulate the in vivo tissue structure, gene expression, and metabolism of tumors, making 3D sphere models increasingly popular in cancer research. Previous studies have shown that 3D culture displays various in vivo tumor features, such as cell-cell/ECM interactions, drug penetrance, dose-response, and drug resistance. Similar to solid tumors, spheroids consist of an external cell proliferation zone, intermediate quiescent cells, and an internal necrotic core, which are exposed to hypoxic conditions. These similarities indicate that 3D models will help better evaluate drug safety and aid in the successful identification of anti-tumor compounds.