Ganglioside GM3 in the Tumor Microenvironment: Mechanisms of Signaling Regulation and Strategies for Angiogenesis Inhibition

Ganglioside GM3, a fundamental glycosphingolipid on the mammalian cell surface, is a key regulator of transmembrane signaling and cellular recognition. In oncology, GM3 acts as a tumor suppressor by modulating the activity of various receptor tyrosine kinases (RTKs) and their downstream pathways. Recent studies highlight its function in the tumor microenvironment (TME), specifically its ability to impede pathological angiogenesis. This review summarizes the molecular mechanisms by which GM3 interferes with pro-angiogenic signaling, such as the VEGF/VEGFR axis, and discusses how this inhibition can be used for therapy. We explore the clinical potential of GM3-based strategies, including monoclonal antibodies and cancer vaccines, discussing the potential of targeting GM3 to reshape the TME and suppress tumor-associated vascularization.