Abstract
Purpose of Review Thrombospondin-2 (THBS2), an extracellular matrix (ECM) regulator, plays a multifaceted role in tumorigenesis. This review systematically summarizes recent advances regarding THBS2 in gastrointestinal tumors (including gastric, colorectal, pancreatic, and liver cancers) and evaluates its potential as a key player in the tumor microenvironment (TME), immune regulation, and clinical diagnostics and therapeutics. Recent Findings THBS2 promotes tumor proliferation and migration by activating the MAPK/PI3K/AKT pathway via integrins. It remodels the t TIVIE through a TGF-(31-THBS2 feedback loop involving cancer-associated fibroblasts (CAFs). Furthermore, THBS2 facilitates metastasis and immune evasion by modulating ECM structure and cytoskeletal dynamics. Emerging therapeutic strategies aim to block THBS2 interactions with CD36/CD47 to enhance anti-PD-1 immunotherapy, disrupt the TGF-f-THBS2 signaling axis, or combine with matrix metalloproteinase (1VIlVIP) inhibitors to suppress fibrosis and tumor dissemination. Summary THBS2 acts as a critical regulator in the pathogenesis and progression of digestive tract tumors. Translating THBS2 into clinical practice requires addressing its context-dependent dual nature, tumor heterogeneity, and potential off-target resistance.