MDK (midkine) encodes a secreted cytokine and growth factor that functions as a key mediator of cell-cell communication in tumor microenvironments. The protein binds to cell-surface proteoglycan receptors and activates multiple signaling pathways including PI3K-AKT and MAPK cascades 1. In cancer contexts, MDK promotes tumor progression through several mechanisms: it facilitates immune evasion by creating immunosuppressive environments enriched with regulatory T cells 2, drives epithelial-to-mesenchymal transition and metastasis 3, and enhances treatment resistance including osimertinib resistance in lung cancer 4. MDK expression increases with age and contributes to age-related cancer susceptibility by activating PI3K-AKT-SREBF1 pathways in mammary tissue 1. The protein acts through various receptor interactions, including MDK-SDC1 and MDK-LRP1 signaling axes, to promote tumor cell proliferation, migration, and invasion 35. Clinically, elevated MDK levels in plasma and cerebrospinal fluid correlate with poor patient outcomes and are associated with leptomeningeal metastases 4. MDK represents a promising therapeutic target, as its suppression reduces treatment resistance and inhibits tumor growth in preclinical models 6.