NOTCH1 as a Radioligand Therapy Target

NOTCH1, notch receptor 1, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, NOTCH1 staining is highest in colorectal cancer (100% of samples positive), head and neck cancer (100% of samples positive) and ovarian cancer (100% of samples positive). Published literature reports that NOTCH1 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 1, any modality).

Is NOTCH1 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: High IHC staining in colorectal cancer, 100% of samples positive.
• ✅ Internalization: Reported to internalize, which favors radionuclide retention.
• ✅ Clinical precedent: Clinical-stage (up to phase 1, any modality)
• ❔ Shedding: Not yet assessed.
• ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.

NOTCH1 expression in cancer

Protein expression of NOTCH1 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.

Is NOTCH1 internalized?

Yes. S1P rapidly activates Notch1 by stimulating the G-coupled protein receptor, S1P Receptor 1 (S1PR1) to drive internalization of the Notch ligand Delta-like protein 4 (Dll4). Notably, this internalization of Dll4 and subsequent activation of Notch does not involve traditional G-protein signaling; instead, S1P-bound S1PR1 forms a complex with Dll4 via the scaffolding protein MPDZ, and the undergoes co-endocytosis.

Sources: PMID 42239339 · PMID 41644301 · PMID 41546116 · PMID 41492187 · PMID 40791532. AI-extracted from abstracts, so verify before citing.

NOTCH1 clinical trials

Clinical-stage (up to phase 1, any modality). Nuclens hasn't indexed trials for NOTCH1 yet. Search ClinicalTrials.gov for NOTCH1 trials.

NOTCH1 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 NOTCH1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.

NOTCH1 gene essentiality (DepMap)

CRISPR knockout effect across 1258 cancer cell lines: -0.00 (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.

Related colorectal cancer radioligand targets

c-MET (MET) · HER3 (ERBB3) · FAP · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2

See all radioligand therapy targets in colorectal cancer.

Data sources

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.