Ou et al. established that regorafenib is capable of inducing the p38MAPK/Creb1/Klf4 signaling pathway responsible for the activation of tumor-associated macrophages [44], and subsequent production of pro-inflammatory cytokines (IL-10, IL-12 and IL-23) responsible for activation of cytotoxic T cells [45]. Here, CREB1 is linked to neoplasm.