Recent mechanistic studies have shown that TIMP-2 and other extracellular matrix regulators enhance 5-FU resistance through JAK-STAT activation [19], while STAT3 hyperactivation, driven by IL-6 trans-signaling or lncRNA dysregulation, confers reduced sensitivity to oxaliplatin and fosters more aggressive tumor phenotypes [20,22,29,38,39,40,41,42]. Here, IL6 is linked to neoplasm.