The Galectin Family in Colorectal Cancer: Integrating Molecular Mechanisms with Diagnostic, Prognostic, and Therapeutic Perspectives

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Increasing evidence indicates that alterations in glycosylation and glycan-binding proteins, such as galectins, contribute substantially to colorectal carcinogenesis. We review the current knowledge on the role of known human galectins in CRC to provide up-to-date summaries, focusing on their involvement in tumor initiation, progression, invasion, angiogenesis, immune evasion, and treatment resistance, integrating molecular mechanisms with diagnostic, prognostic, and therapeutic perspectives. Methods: We searched for “colorectal cancer” and “Galectin”, “Galectin-X” and “colorectal cancer”, and “Gal-X” and “colorectal cancer” (X denotes the number of the respective galectin) in PubMed, ScienceDirect, Scopus, and Web of Science databases. All records were screened for relevance by the authors. Results: We summarize the expression patterns of individual galectins in colorectal tissues and circulation, their involvement in oncogenic signaling pathways, and their interactions with the tumor microenvironment. Furthermore, we critically evaluate the available evidence regarding their diagnostic, prognostic, and therapeutic potential. Conclusions: Although galectin-1 and galectin-3 are the most extensively investigated galectins, accumulating evidence suggests that galectin-4, galectin-8, and galectin-9 also play important context-dependent roles in CRC progression and immune regulation. However, methodological heterogeneity and limited clinical validation currently preclude the implementation of galectins as standalone biomarkers in routine practice. Future research should focus on standardized multicenter studies, clarification of context-dependent galectin functions, and the development of galectin-targeted therapies. A deeper understanding of galectin biology may facilitate the development of novel multimarker diagnostic approaches and personalized therapies for CRC patients.