Abbreviated name: DLL3

Synonyms: SCDO1

Compound class: Endogenous peptide in human, mouse or rat

Comment: DLL3 is is an inhibitory NOTCH pathway ligand. The mature protein is 592 amino acids long and contains DSL and transmembrane domains, and EGF repeats that are characteristic of NOTCH family ligands. DLL3 can be detected in the cytoplasm of a few normal adult cell types (neurons, pancreatic islet cells, pituitary cells). In contrast, its expression is highly upregulated to the surface of malignant cells of neuroendocrine origin, including small cell lung cancer (SCLC) [4-5], melanoma, glioblastoma multiforme, small cell bladder cancer, metastatic castration-resistant prostate cancer, and neuroendocrine lung tumours, and is detected on cancer stem cells. Its favourable expression profile has enabled DLL3-targeted therapeutic development for these cancer indications [2-3]. To date, DLL3-targeted therapies include an antibody-drug conjugate (rovalpituzumab tesirine; max phase 3, development terminated), a bispecific T cell engager (tarlatamab, formerly AMG757; max phase 3) and a chimeric antigen receptor T cell therapy (AMG119; max phase 1), all of which were first evaluated in advanced SCLC.

Species: Human