DLL3 as a Radioligand Therapy Target
DLL3, delta like canonical Notch ligand 3, is a cell-surface protein. No tumor protein staining is recorded for it in Human Protein Atlas immunohistochemistry. Evidence on whether DLL3 internalizes is mixed. Clinical status: Clinical-stage (up to phase 3, any modality), with 1 active clinical trial.
Is DLL3 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ❌ Tumor expression: No tumor staining in HPA immunohistochemistry.
- ⚠️ Internalization: Mixed evidence.
- ✅ Clinical precedent: Clinical-stage (up to phase 3, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
DLL3 expression in cancer
No Human Protein Atlas tumor immunohistochemistry data is available for DLL3.
Is DLL3 internalized?
Uncertain. The first abstract mentions DLL3 as an emerging cell surface receptor that may support next-generation targeted drug delivery platforms but does not provide direct evidence of internalization or endocytosis upon binding. The second abstract discusses a DLL3-targeting ADC but lacks specific information about whether DLL3 undergoes endocytosis or internalization upon binding, leaving the evidence ambiguous.
Sources: PMID 41900872 · PMID 39143619 · PMID 38940283 · PMID 18676613 · PMID 16000382. AI-extracted from abstracts, so verify before citing.
DLL3 clinical trials
Clinical-stage (up to phase 3, any modality). 1 active trial reference DLL3 (ClinicalTrials.gov, accessed 2026-09-28).
DLL3 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See DLL3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
DLL3 gene essentiality (DepMap)
CRISPR knockout effect across 1255 cancer cell lines: -0.07 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.