ROS1 as a Radioligand Therapy Target
ROS1, ROS proto-oncogene 1, receptor tyrosine kinase, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, ROS1 staining is highest in pancreatic cancer (36% of samples positive), head and neck cancer (50% of samples positive) and colorectal cancer (25% of samples positive). Evidence on whether ROS1 internalizes is mixed. Clinical status: Clinical-stage (up to phase 3, any modality).
Is ROS1 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: Low IHC staining in pancreatic cancer, 36% of samples positive.
- ⚠️ 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.
ROS1 expression in cancer
Protein expression of ROS1 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 | 0.18 | Low | 36% |
| Head and Neck Cancer | 0.17 | Low | 50% |
| Colorectal Cancer | 0.17 | Low | 25% |
| Skin Cancer | 0.11 | Low | 25% |
| Melanoma | 0.11 | Low | 25% |
| Liver Cancer | 0.11 | Low | 17% |
| Kidney Cancer | 0.03 | Low | 8% |
| Gastric Cancer | 0.03 | Low | 8% |
Not detected by IHC in: ovarian cancer, lymphoma, breast cancer, thyroid cancer, bladder cancer, neuroendocrine tumors, cervical cancer, lung cancer, prostate cancer, testicular cancer, endometrial cancer, glioma.
Is ROS1 internalized?
Uncertain. The abstract discusses HER3's internalization rate and its association with payload release after HER3-DXd treatment but does not provide direct information about ROS1 or its internalization upon ligand/antibody binding.
Sources: PMID 41752065. AI-extracted from abstracts, so verify before citing.
ROS1 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for ROS1 yet. Search ClinicalTrials.gov for ROS1 trials.
ROS1 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 ROS1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
ROS1 gene essentiality (DepMap)
CRISPR knockout effect across 1249 cancer cell lines: 0.11 (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.
See how ROS1 ranks against 15,000 targets for your indication.
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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.