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.
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.
- 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
2 products aim at DLL3: antibody-drug conjugates and bispecific antibodies. 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.
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 common it is, by cancer
| 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.
Rovalpituzumab tesirine (Rova-T) was the first drug against DLL3 in small-cell lung cancer. AbbVie bought it for $5.8B and abandoned it after two failed phase 3 trials. The target later worked with a different weapon.
The first T-cell engager to improve survival in a common solid tumour, small-cell lung cancer.
Latest papers
topQuery for this target: (TITLE:"DLL3" OR ABSTRACT:"DLL3") AND (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.
Pages like this
not linked directly; found by shared links- TargetCD3
Shares DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer, Tarlatamab, T-cell engagers (bispecific) and the tag t-cell-engager-target.
- TargetGPRC5D
Shares T-cell engagers (bispecific) and the tag t-cell-engager-target.
- TargetKLK2 (kallikrein-2)
Shares Prostate cancer and the tag t-cell-engager-target.
- TargetSTEAP1
Shares Prostate cancer and the tag t-cell-engager-target.
- TargetBCMA
Shares Hospital Universitario 12 de Octubre, Resistance routes: how a blocked pathway comes back, T-cell engagers (bispecific) and the tag t-cell-engager-target.
- TermHistologic transformation
Shares Hallmark (2022): unlocking phenotypic plasticity, Cancer stem cells & phenotypic plasticity, Lineage plasticity & neuroendocrine transformation, Resistance routes: how a blocked pathway comes back.
- ProductIfinatamab deruxtecan
Shares Sequencing DLL3 engager and B7-H3 ADC in relapsed SCLC, Lineage plasticity & neuroendocrine transformation, Small-cell lung cancer, Prostate cancer.
- PairingChemo-immunotherapy induction → maintenance intensification (SCLC)
Shares DeLLphi-305, Tarlatamab, Small-cell lung cancer.