Gastrointestinal neuroendocrine tumors (GI-NETs) lack effective targeted options beyond somatostatin analogs and mTOR inhibitors. Spleen tyrosine kinase (SYK) is a non-receptor kinase with emerging roles in solid tumors and available small-molecule inhibitors. We explored whether SYK is a plausible therapeutic target in GI-NET using two human cell lines. SYK expression in GI-NET cells was confirmed by immunofluorescence. Cells were exposed to a selective SYK inhibitor (BI-1002494), and proliferation was quantified using both 2D and 3D models. Both GI-NET models expressed SYK and exhibited reduced growth upon SYK blockade, with dose-dependent suppression of viability and increased cytotoxicity relative to vehicle. In spheroid assays, morphologic changes and reduced size were observed. These pilot data suggest SYK as a targetable vulnerability in GI-NET and support formal dose-response studies, genetic validation, and combination strategies with standard-of-care agents. Given the clinical availability of SYK inhibitors, these findings provide a rationale for translational studies in GI-NET.
