ALK
A gene fusion found in about 5% of lung cancers that responds spectacularly to pills, now for many years.
ALK rearrangements occur in ~4-5% of NSCLC, typically in younger never-smokers. Lorlatinib achieved 5-year PFS of ~60% in CROWN, the longest of any targeted therapy in metastatic NSCLC. Alectinib is approved in the adjuvant setting (ALINA). Fourth-generation inhibitors (neladalkib) address compound resistance mutations.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A gene fusion found in about 5% of lung cancers that responds spectacularly to pills, now for many years.
- 1 · What it is
A gene fusion found in about 5% of lung cancers that responds spectacularly to pills, now for many years.
- 2 · What goes wrong in cancer
ALK is a receptor tyrosine kinase; the EML4-ALK fusion is most common. It is also altered in anaplastic large-cell lymphoma and neuroblastoma.
- 3 · How drugs use it
8 products aim at ALK: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
ALK is a receptor tyrosine kinase; the EML4-ALK fusion is most common. It is also altered in anaplastic large-cell lymphoma and neuroblastoma.
- NSCLC (~5%)
- Anaplastic large-cell lymphoma
- Neuroblastoma
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Neuroblastoma | 8-14% | Activating mutation/amplification | Higher at relapse | Wikipedia |
| Non-small-cell lung cancer | 3-5% | Rearrangement | Younger never-smokers | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
Brigatinib is an ALK pill with strong brain activity, approved first after crizotinib and then first line after beating it in ALTA-1L.
Ceritinib is a second-generation ALK pill for lung cancer, effective after crizotinib but with gastrointestinal toxicity that limited uptake.
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
A Chinese-developed ALK pill approved in the US in December 2024 for first-line ALK-positive lung cancer.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
A fourth-generation ALK pill that works after lorlatinib and avoids the TRK-related brain side effects; under FDA priority review with a decision due 27 November 2026.
Latest papers
topQuery for this target: (TITLE:"ALK" OR ABSTRACT:"ALK") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ALK, not a curated reading list.