CAIX (CA9) as a Radioligand Therapy Target
CAIX (CA9), carbonic anhydrase 9, is a cell-surface protein. In Human Protein Atlas immunohistochemistry, CAIX staining is highest in kidney cancer (50% of samples positive), gastric cancer (36% of samples positive) and bladder cancer (27% of samples positive). Published literature suggests CAIX does not readily internalize, so radionuclide retention may rely on surface binding. Clinical status: Clinical-stage (up to phase 3, any modality), with 2 active clinical trials.
Is CAIX 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: Medium IHC staining in kidney cancer, 50% of samples positive.
- ❌ Internalization: Reported not to internalize.
- ✅ 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.
CAIX expression in cancer
Protein expression of CAIX 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 |
|---|---|---|---|
| Kidney Cancer | 0.31 | Medium | 50% |
| Gastric Cancer | 0.21 | Medium | 36% |
| Bladder Cancer | 0.12 | Low | 27% |
| Liver Cancer | 0.06 | Low | 9% |
| Pancreatic Cancer | 0.03 | Low | 10% |
| Cervical Cancer | 0.03 | Low | 9% |
Not detected by IHC in: skin cancer, colorectal cancer, head and neck cancer, ovarian cancer, lymphoma, breast cancer, melanoma, thyroid cancer, neuroendocrine tumors, lung cancer, prostate cancer, testicular cancer, endometrial cancer, glioma.
Is CAIX internalized?
No. CA9 is involved in the inhibition of transferrin endocytosis, suggesting that it does not undergo internalization itself.
Sources: PMID 36760347 · PMID 33225555. AI-extracted from abstracts, so verify before citing.
CAIX clinical trials
Clinical-stage (up to phase 3, any modality). 2 active trials reference CAIX (ClinicalTrials.gov, accessed 2026-06-29).
CAIX 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 CAIX in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
CAIX gene essentiality (DepMap)
CRISPR knockout effect across 1254 cancer cell lines: -0.08 (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 kidney cancer radioligand targets
EGFR · c-MET (MET) · HER3 (ERBB3) · STEAP2 · ITGAV · Mesothelin (MSLN) · SSTR2 · HER2 (ERBB2)
See all radioligand therapy targets in kidney 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.