ESR1 as a Radioligand Therapy Target
ESR1, estrogen receptor 1, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, ESR1 staining is highest in breast cancer (70% of samples positive), endometrial cancer (46% of samples positive) and ovarian cancer (42% of samples positive). Published literature reports that ESR1 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is ESR1 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 breast cancer, 70% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ 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.
ESR1 expression in cancer
Protein expression of ESR1 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 |
|---|---|---|---|
| Breast Cancer | 0.70 | High | 70% |
| Endometrial Cancer | 0.33 | Medium | 46% |
| Ovarian Cancer | 0.28 | Medium | 42% |
| Prostate Cancer | 0.06 | Low | 18% |
| Skin Cancer | 0.03 | Low | 8% |
Not detected by IHC in: colorectal cancer, head and neck cancer, lymphoma, melanoma, kidney cancer, thyroid cancer, bladder cancer, neuroendocrine tumors, cervical cancer, lung cancer, pancreatic cancer, gastric cancer, testicular cancer, glioma, liver cancer.
Is ESR1 internalized?
Yes. Chronic exposure to CAP, however, may result in downregulation and internalization of ESR1.
Sources: PMID 40003617 · PMID 27528396. AI-extracted from abstracts, so verify before citing.
ESR1 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for ESR1 yet. Search ClinicalTrials.gov for ESR1 trials.
ESR1 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 ESR1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
ESR1 gene essentiality (DepMap)
CRISPR knockout effect across 1257 cancer cell lines: -0.05 (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 breast cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · FAP · HER2 (ERBB2) · STEAP2 · EGFR · B7-H3 (CD276) · SSTR2
See all radioligand therapy targets in breast 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.