Anaplastic Lymphoma Kinase (ALK)
ALK receptor tyrosine kinase is a receptor tyrosine kinase encoded by the ALK gene and is best known in medicine as a clinically important oncogenic target in several cancers, especially ALK-rearranged non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma.
ALK receptor tyrosine kinase is a receptor tyrosine kinase encoded by the ALK gene and is best known in medicine as a clinically important oncogenic target in several cancers, especially ALK-rearranged non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma. In normal biology, ALK is a membrane-associated signaling protein, but in cancer it is most often relevant through gene rearrangements/fusions that lead to constitutive kinase activation and downstream proliferative and survival signaling.
Because ALK-driven tumors can be highly dependent on this signaling axis, ALK has become a major target for ALK-tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib, and lorlatinib. These agents have transformed treatment of ALK-positive NSCLC, including disease with central nervous system involvement, but resistance remains a major clinical challenge. Recent research also continues to use ALK status as a diagnostic and stratification marker in other tumors, including inflammatory myofibroblastic tumor and anaplastic large cell lymphoma.
Where the papers sit
15 papers from the last 6 months study Anaplastic Lymphoma Kinase (ALK) directly · updated from PubMed 1 Oct 2026
Study type 0 clinical trials · 3 observational · 2 human data · 8 preclinical · 2 unclassified
Themes 3 themes · 1 new direction
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ALK-Positive Lung Cancer
ALK-positive lung cancer treatment is moving toward potent, brain-penetrant next-generation TKIs and molecularly targeted alternatives. Lorlatinib, alectinib and brigatinib recur in real-world, economic and pharmacokinetic studies, while resistance after second-generation TKIs remains a major problem. Gilteritinib and the molecular glue degrader TRI-611 represent efforts to overcome resistance or eliminate ALK more directly. Toxicity, immune correlates, treatment cost and central nervous system control remain important unresolved endpoints.
10 papers · 66.7%
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ALK Drug Development
ALK drug development is balancing tumor control, resistance evolution and clinically relevant drug exposure. Protein degraders and modular sila-pharmacophores broaden the search beyond conventional kinase inhibition, while dose modeling addresses how treatment intensity may shape resistance. Drug–drug interaction work, including nicardipine effects on entrectinib metabolism, highlights pharmacokinetic constraints. The studies share optimization goals but do not establish a single preferred strategy.
3 papers · 20%
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Anaplastic Large-Cell Lymphoma
Anaplastic large-cell lymphoma involving the mouth is characterized through oral lesions, clinicopathology and immunophenotyping. The reported cases emphasize the diagnostic challenge of recognizing lymphoma in gingival and other oral presentations. Experimental work is also testing triazole-dithiocarbamate compounds to enhance cytarabine efficacy and selectivity. The field remains focused on better recognition and early therapeutic validation rather than an established treatment shift.
2 papers · 13.3%
ALK is implicated as a microglial driver of Parkinson-related neuroinflammation, not only as a cancer target
The MPTP-induced mouse model of Parkinson’s disease treated with lorlatinib assumes ALK primarily as a therapeutic target in ALK-driven malignancy, whereas this study found that ALK phosphorylation was concentrated in microglia and that ALK inhibition reduced neuroinflammation, oxidative stress, dopaminergic neuronal loss, and motor impairment. This extends ALK into a disease mechanism outside cancer and identifies it as a potential target for neurodegenerative disease intervention 42208344May.
Papers
The 15 papers from the last 6 months that study Anaplastic Lymphoma Kinase (ALK) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
ALK-Positive Lung Cancer (10)
- Severe, reversible alectinib-induced acute kidney injury requiring dialysis in an elderly patient with metastatic non-small cell lung cancer. BMJ case reports · 22 Sept 2026 PMID 42772921
- TRI-611, a selective, brain-penetrant molecular glue degrader of ALK. Nature · 10 Sept 2026 PMID 42717093
- Physiologically Based Pharmacokinetic Model of Brigatinib in Healthy Volunteers and Patients With Cancer. CPT: pharmacometrics & systems pharmacology · 21 Jul 2026 PMID 42481921
- Real-World Clinical and Economic Consequences of Next-Generation Anaplastic Lymphoma Kinase-Positive (ALK +) Tyrosine Kinase Inhibitors (TKIs) in Patients with TKI-Naïve ALK + Metastatic Non-Small Cell Lung Cancer in the United States. Advances in therapy · 9 Jul 2026 PMID 42423952
- [Translated article] Real world outcomes of first-line pembrolizumab in metastatic non-small-cell lung cancer. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria · 12 Jun 2026 PMID 42285782
- Lorlatinib protects dopaminergic neurons by inhibiting ALK-mediated neuroinflammation in a mouse model of Parkinson's disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 28 May 2026 PMID 42208344
- Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression. International journal of molecular medicine · 30 Apr 2026 PMID 42059267
- Cost-effectiveness analysis of lorlatinib as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer in Italy. Journal of medical economics · 27 Apr 2026 PMID 42043888
- Fragment-based discovery of pyrazole-5-carboxamide derivatives as ALK inhibitors against non-small cell lung cancer. Bioorganic chemistry · 23 Apr 2026 PMID 42025599
- Immune-related gene expression profiling and alectinib efficacy for patients with ALK-Rearranged non-small cell lung cancer: exploratory analysis of a prospective observational study. Lung cancer (Amsterdam, Netherlands) · 21 Apr 2026 PMID 42013562
ALK Drug Development (3)
- Varying Cancer Drug Doses to Balance Tumor Control and Resistance Evolution. Cancer research · 2 Sept 2026 PMID 42682083
- Evaluation of the Effects of Nicardipine on Entrectinib Metabolism in vitro and in Rats. European journal of drug metabolism and pharmacokinetics · 2 Jun 2026 PMID 42230445
- Bringing Silicon to Drugs: Modular Construction of Sila-Pharmacophores for the Development of Target Protein Degraders. Journal of the American Chemical Society · 23 Apr 2026 PMID 42024006
Anaplastic Large-Cell Lymphoma (2)
- Oral manifestations of anaplastic large cell lymphoma: clinicopathological features and main immunophenotypic findings of 3 cases. Journal of hematopathology · 29 May 2026 PMID 42213355
- A novel triazole-dithiocarbamate hybrid synergistically enhances cytarabine efficacy and selectivity in anaplastic large cell lymphoma. Bioorganic chemistry · 12 May 2026 PMID 42119208
By study type
Observational studies and case reports (3)
- Severe, reversible alectinib-induced acute kidney injury requiring dialysis in an elderly patient with metastatic non-small cell lung cancer. BMJ case reports · 22 Sept 2026 PMID 42772921
- Oral manifestations of anaplastic large cell lymphoma: clinicopathological features and main immunophenotypic findings of 3 cases. Journal of hematopathology · 29 May 2026 PMID 42213355
- Immune-related gene expression profiling and alectinib efficacy for patients with ALK-Rearranged non-small cell lung cancer: exploratory analysis of a prospective observational study. Lung cancer (Amsterdam, Netherlands) · 21 Apr 2026 PMID 42013562
Human data, design not indexed (2)
- Physiologically Based Pharmacokinetic Model of Brigatinib in Healthy Volunteers and Patients With Cancer. CPT: pharmacometrics & systems pharmacology · 21 Jul 2026 PMID 42481921
- Cost-effectiveness analysis of lorlatinib as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer in Italy. Journal of medical economics · 27 Apr 2026 PMID 42043888
Preclinical: animal, cell and lab studies (8)
- TRI-611, a selective, brain-penetrant molecular glue degrader of ALK. Nature · 10 Sept 2026 PMID 42717093
- Varying Cancer Drug Doses to Balance Tumor Control and Resistance Evolution. Cancer research · 2 Sept 2026 PMID 42682083
- Evaluation of the Effects of Nicardipine on Entrectinib Metabolism in vitro and in Rats. European journal of drug metabolism and pharmacokinetics · 2 Jun 2026 PMID 42230445
- Lorlatinib protects dopaminergic neurons by inhibiting ALK-mediated neuroinflammation in a mouse model of Parkinson's disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 28 May 2026 PMID 42208344
- A novel triazole-dithiocarbamate hybrid synergistically enhances cytarabine efficacy and selectivity in anaplastic large cell lymphoma. Bioorganic chemistry · 12 May 2026 PMID 42119208
- Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression. International journal of molecular medicine · 30 Apr 2026 PMID 42059267
- Fragment-based discovery of pyrazole-5-carboxamide derivatives as ALK inhibitors against non-small cell lung cancer. Bioorganic chemistry · 23 Apr 2026 PMID 42025599
- Bringing Silicon to Drugs: Modular Construction of Sila-Pharmacophores for the Development of Target Protein Degraders. Journal of the American Chemical Society · 23 Apr 2026 PMID 42024006
Unclassified: not yet indexed with MeSH (2)
- Real-World Clinical and Economic Consequences of Next-Generation Anaplastic Lymphoma Kinase-Positive (ALK +) Tyrosine Kinase Inhibitors (TKIs) in Patients with TKI-Naïve ALK + Metastatic Non-Small Cell Lung Cancer in the United States. Advances in therapy · 9 Jul 2026 PMID 42423952
- [Translated article] Real world outcomes of first-line pembrolizumab in metastatic non-small-cell lung cancer. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria · 12 Jun 2026 PMID 42285782
Written from 15 PubMed abstracts, each one listed by PMID above. Published: 2026-06-16. Last written: 2026-09-24 by GPT. Drafted by language models from published abstracts; not medical advice.