CXCR4 and cancer: The SDF1/CXCR4 pathway is a major signaling axis that contributes to resistance in pancreatic cancer; SDF1 is secreted by CAFs and interacts with CXCR4, its receptor, which is present on the cancer cells, and induces gemcitabine chemoresistance in these cells by paracrine-induced activation of the intracellular FAK-AKT and ERK1/2 signaling pathways and a subsequent autocrine IL-6 signaling loop (Zhang et al., 2015).