CXCR4 and neoplasm: The HIF-1 pathway [257], PI3K-PTEN-AKT pathway [258, 259], and loss of serine/threonine liver kinase B1 (LKB1) [260] are the mechanisms involved in the recruitment and activation of tumor-associated macrophages (TAMs) into solid tumors, usually through CXCL12 and CCL2 engagement with their receptors CXCR4 and CCR2, respectively.