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<p>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.</p>

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Spleen tyrosine kinase (SYK) inhibition suppresses growth of gastrointestinal neuroendocrine tumor cells: a pilot study in two cell lines

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月16日

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  • Angeliki Ditsiou,
  • Lara Toffoli,
  • Viviana Vella,
  • Francesca D’Este,
  • Teresa Gagliano

摘要

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.