CXCL12 and neoplasm: Second, regarding treatment resistance mechanisms, CAFs exert effects through three pathways: (1) The physical barrier constructed by myCAFs significantly reduces the effective concentration of chemotherapeutic drugs within tumor tissue; (2) Bypass signaling pathways provided by iCAFs, such as HGF/c-MET, enable tumor cells to evade drug-induced apoptosis; (3) Factors secreted by CAFs, such as CXCL12 and TGF-β, recruit immunosuppressive cells and inhibit T-cell function, limiting the efficacy of immunotherapy (33).