In this context, our discovery of the DCLK1/XRCC5/COX2 axis in mouse models of both colorectal cancer (Figure 4) and breast cancer (Figure S9) suggests a new clue for mechanistic insight into the TME-regulating role of CSCs and may broaden the preclinical rationale for expanding the clinical trials of DCLK1 inhibitors for cancer treatment. Here, XRCC5 is linked to breast cancer.