DLL3
A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them.
Overview
Delta-like ligand 3 is an inhibitory Notch ligand aberrantly surface-expressed in ~85% of small-cell lung cancer and neuroendocrine prostate cancer. The first DLL3 ADC (rovalpituzumab tesirine) failed; the T-cell engager tarlatamab (Imdelltra) succeeded, with a survival benefit in second-line SCLC (DeLLphi-304). Trispecifics and CAR-T follow. For radiopharmaceuticals it is a target in waiting rather than in use: no DLL3 radioligand is in the clinic, and the nearest commitment is the discovery-stage DLL3 programme Telix acquired from ImaginAb in January 2025, which carries no candidate code or isotope. A surface antigen present on most small-cell lung cancers, in a disease where a scan-then-treat pair does not yet exist, is the obvious place for one.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them.
- 1 · What it is
A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them.
- 2 · What goes wrong in cancer
Normally intracellular Golgi protein; ASCL1-driven neuroendocrine lineage exposes it on the membrane.
- 3 · How drugs use it
No product in this corpus aims at DLL3 yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
Biology
Normally intracellular Golgi protein; ASCL1-driven neuroendocrine lineage exposes it on the membrane.
- Small-cell lung cancer
- Neuroendocrine prostate cancer
- Large-cell neuroendocrine carcinoma
How often this target appears
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Small-cell lung cancer | 80-85% | IHC, any expression | Wikipedia | |
| Prostate cancer | 70-80% | Neuroendocrine prostate cancer only | Rare in adenocarcinoma | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Latest papers
topQuery for this target: (TITLE:"DLL3" OR ABSTRACT:"DLL3") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DLL3, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetKLK2 (kallikrein-2)
Shares Prostate cancer and the tag t-cell-engager-target.
- TargetSTEAP1
Shares Prostate cancer and the tag t-cell-engager-target.
- TargetB7-H3
Shares Lineage plasticity & neuroendocrine transformation, Small-cell lung cancer, Prostate cancer.
- TrialPSMA PET Combined With MRI for the Detection of PCa
Shares Telix Pharmaceuticals, Prostate cancer.
- TrialStudy of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors
- PathwayProstate cancer (KEGG map)
Shares Lineage plasticity & neuroendocrine transformation, Prostate cancer.
- AgentLutetium-177 rosopatamab tetraxetan
- CompanyEvergreen Theragnostics