Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, mainly due to late diagnosis and high metastatic potential. Effective management requires accurate diagnostic, prognostic, and therapeutic strategies, with growing focus on molecular biomarkers. Chemokines, which are small, secreted proteins regulating immune cell migration and tissue homeostasis, shape the tumor microenvironment by promoting tumor growth, angiogenesis, immune evasion, and metastasis. In CRC, the expression of altered chemokine-receptor profiles correlates with progression and clinical outcomes. Chemokines are classified by the presence or absence of the ELR motif, which differentiates CXC subgroups. Selection focused on those consistently altered in CRC tissues or serum and involved in key oncogenic processes. CXCL1 and its receptor CXCR2 are overexpressed and linked to tumor progression, highlighting their diagnostic and therapeutic potential. CXCL8 is elevated in tissues and serum, correlating with metastasis and poor survival. The CXCL12/CXCR4/CXCR7 axis drives metastasis. CXCL13 promotes immune evasion via CXCR5, while CXCL14 is downregulated, suggesting a protective role. Moreover, CXCL16 associates with worse outcomes, whereas CXCR6 may enhance immunotherapy response. Overall, chemokines and receptors are promising blood biomarkers and therapeutic targets in CRC. Further validation is needed using large prospective studies, standardized assays, and multi-marker approaches to establish their potential as non-invasive CRC biomarkers.