delta like canonical Notch ligand 3   Click here for help

GtoPdb Ligand ID: 10560

Abbreviated name: DLL3
Synonyms: SCDO1
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
1. Giffin MJ, Cooke K, Lobenhofer EK, Estrada J, Zhan J, Deegen P, Thomas M, Murawsky CM, Werner J, Liu S et al.. (2021)
AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer.
Clin Cancer Res, 27 (5): 1526-1537. [PMID:33203642]
2. Leonetti A, Facchinetti F, Minari R, Cortellini A, Rolfo CD, Giovannetti E, Tiseo M. (2019)
Notch pathway in small-cell lung cancer: from preclinical evidence to therapeutic challenges.
Cell Oncol (Dordr), 42 (3): 261-273. [PMID:30968324]
3. Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM et al.. (2019)
Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study.
Clin Cancer Res, 25 (23): 6958-6966. [PMID:31506387]
4. Owen DH, Giffin MJ, Bailis JM, Smit MD, Carbone DP, He K. (2019)
DLL3: an emerging target in small cell lung cancer.
J Hematol Oncol, 12 (1): 61. [PMID:31215500]
5. Xie H, Boland JM, Maleszewski JJ, Aubry MC, Yi ES, Jenkins SM, Koepplin JW, Terra SBSP, Mansfield AS, Roden AC. (2019)
Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors.
Lung Cancer, 135: 73-79. [PMID:31447005]