ITPR3 as a Radioligand Therapy Target
ITPR3, inositol 1,4,5-trisphosphate receptor type 3, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, ITPR3 staining is highest in pancreatic cancer (100% of samples positive), colorectal cancer (100% of samples positive) and head and neck cancer (100% of samples positive). Published literature reports that ITPR3 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is ITPR3 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 pancreatic cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
ITPR3 expression in cancer
Protein expression of ITPR3 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.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Pancreatic Cancer | 0.83 | High | 100% |
| Colorectal Cancer | 0.76 | High | 100% |
| Head and Neck Cancer | 0.75 | High | 100% |
| Gastric Cancer | 0.73 | High | 100% |
| Lung Cancer | 0.72 | High | 100% |
| Bladder Cancer | 0.69 | High | 100% |
| Breast Cancer | 0.67 | High | 100% |
| Thyroid Cancer | 0.67 | High | 100% |
| Endometrial Cancer | 0.67 | High | 100% |
| Skin Cancer | 0.64 | High | 100% |
| Cervical Cancer | 0.64 | High | 100% |
| Melanoma | 0.56 | High | 83% |
| Kidney Cancer | 0.55 | High | 91% |
| Ovarian Cancer | 0.42 | Medium | 100% |
| Testicular Cancer | 0.33 | Medium | 100% |
| Prostate Cancer | 0.33 | Medium | 82% |
| Liver Cancer | 0.31 | Medium | 42% |
| Neuroendocrine Tumors | 0.17 | Low | 50% |
| Lymphoma | 0.06 | Low | 17% |
| Glioma | 0.06 | Low | 17% |
Is ITPR3 internalized?
Yes. the observed Ca(2+) influx is supported by ORAI calcium release-activated calcium modulator 1 (Orai1) and stromal interaction molecule 1 (STIM1). This result suggests that extracellular Ca(2+) entry, which is required for ROS production, is mediated by a store-operated Ca(2+) mechanism.
Sources: PMID 21239714. AI-extracted from abstracts, so verify before citing.
ITPR3 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for ITPR3 yet. Search ClinicalTrials.gov for ITPR3 trials.
ITPR3 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 ITPR3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
ITPR3 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.09 (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 pancreatic cancer radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · Mesothelin (MSLN) · FAP · CEA (CEACAM5) · STEAP2 · SSTR2
See all radioligand therapy targets in pancreatic cancer.
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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.