Delta-like canonical Notch ligand 3 (DLL3) is an inhibitory protein.1 The Notch pathway is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. DLL3 is typically located in the Golgi apparatus, where it inhibits Notch 1 signaling.2
In high-grade neuroendocrine tumors—including small-cell lung cancer—Notch signaling suppresses tumor growth.2 In these tumors, DLL3 is highly upregulated and aberrantly expressed on the cell surface, while Notch 1 is inactive.2,3 Activating Notch signaling through DLL3 inhibition may be a novel treatment approach for neuroendocrine tumors.
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1. Sabri JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Nat Rev Clin Oncol. 2017;14(9):549-561. 2. Saunders LR, Bankovich AJ, Anderson WC, et al. Sci Transl Med. 2015;7(302):302ra136. doi:10.1126/scitranslmed.aac9459. 3. Kunninmalaiyaan M, Chen H. Oncologist. 2007;12(5):535-542.