ALK as a Radioligand Therapy Target
ALK, ALK receptor tyrosine kinase, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, ALK staining is highest in skin cancer (90% of samples positive), prostate cancer (92% of samples positive) and glioma (83% of samples positive). Evidence on whether ALK internalizes is mixed. Clinical status: Clinical-stage (up to phase 3, any modality), with 4 active clinical trials.
Is ALK 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 skin cancer, 90% 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.
ALK expression in cancer
Protein expression of ALK 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 |
|---|---|---|---|
| Skin Cancer | 0.60 | High | 90% |
| Prostate Cancer | 0.53 | High | 92% |
| Glioma | 0.36 | Medium | 83% |
| Thyroid Cancer | 0.33 | Medium | 100% |
| Pancreatic Cancer | 0.33 | Medium | 100% |
| Bladder Cancer | 0.31 | Medium | 83% |
| Breast Cancer | 0.30 | Medium | 91% |
| Gastric Cancer | 0.30 | Medium | 91% |
| Melanoma | 0.28 | Medium | 67% |
| Head and Neck Cancer | 0.25 | Medium | 75% |
| Testicular Cancer | 0.25 | Medium | 75% |
| Liver Cancer | 0.24 | Medium | 73% |
| Endometrial Cancer | 0.21 | Medium | 55% |
| Colorectal Cancer | 0.19 | Low | 58% |
| Lung Cancer | 0.19 | Low | 58% |
| Ovarian Cancer | 0.18 | Low | 46% |
| Neuroendocrine Tumors | 0.17 | Low | 50% |
| Cervical Cancer | 0.15 | Low | 46% |
| Kidney Cancer | 0.11 | Low | 33% |
| Lymphoma | 0.06 | Low | 17% |
Is ALK internalized?
Uncertain. The abstracts provided do not contain specific information regarding the internalization or endocytosis of the ALK protein upon ligand or antibody binding. The first abstract focuses on HER3 dynamics and its relation to internalization but does not mention ALK directly. The second abstract does not provide relevant information about ALK either.
Sources: PMID 41752065 · PMID 40232352 · PMID 40119140 · PMID 39303527 · PMID 38913441. AI-extracted from abstracts, so verify before citing.
ALK clinical trials
Clinical-stage (up to phase 3, any modality). 4 active trials reference ALK (ClinicalTrials.gov, accessed 2026-09-21).
NCT07826195 · NCT05010109 · NCT07804186 · NCT06985953
ALK 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 ALK in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
ALK gene essentiality (DepMap)
CRISPR knockout effect across 1249 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 skin cancer radioligand targets
EGFR · c-MET (MET) · HER3 (ERBB3) · B7-H3 (CD276) · SSTR2 · ITGB6 · HER2 (ERBB2) · ITGAV
See all radioligand therapy targets in skin 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.