In this study, we observed differences in the efficacy of the anticancer drugs, the growth activity of the cancer cells, and the survival potency in the 3D and the 2D models; these differences led us to investigating the mechanism of the CD44+117+CSCs’ resistance to chemotherapeutic agents when the CD44+117+CSCs were cultured in the 3D and the 2D environments. Here, CD44 is linked to cancer.