Profound connection between atherosclerosis and cancer: The role of galectin-3: A review

Atherosclerosis (AS) and cancer are major chronic diseases that pose considerable threats to human health. AS and cancer share common risk factors and pathogenic mechanisms, including oxidative stress, inflammation, aberrant apoptosis, uncontrolled proliferation, and angiogenesis (the formation of new blood vessels), with profound molecular interconnections. Galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is involved in the regulation of various physiological functions such as the inflammatory microenvironment, cell proliferation, and macrophage polarization in both AS and cancer. Additionally, it regulates signaling pathways such as NF-κB and Wnt/β-catenin, serving as a "bridge molecule" between them. This review explores the bidirectional relationship between AS and cancer, with a focus on Gal-3-mediated molecular crosstalk and the translational potential of Gal-3-targeted diagnostic and therapeutic strategies. The pathways by which Gal-3 drives pathological processes in AS and cancer are summarized, focusing on the intersection points of Gal-3-mediated molecular mechanisms. A series of Gal-3-targeting strategies, including small-molecule carbohydrate inhibitors, natural polysaccharides and their derivatives, peptides, and monoclonal antibodies, have been presented. The mechanism of action, selectivity, and therapeutic potential of Gal-3 in AS and preclinical models of cancer have been discussed along with a summary the results of clinical trials.