ArticleNature cancer2022
Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Pooled it
- NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.Cancer discovery · 2024Trial
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- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Advances in translational lung cancer research in 2025: a narrative review.Translational lung cancer research · 2026Review
- The novel ALK K1150dup mutation mediates resistance to frontline lorlatinib and retains sensitivity to gilteritinib.NPJ precision oncology · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Review
- Article
- A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Genome biology · 2026Article
- Pyrazole in drug development: a medicinal-chemistry based analysis of USFDA-approved drugs in last decade.Molecular diversity · 2026Review
- Pathology of peripheral neuroblastic tumors.Diagnostic pathology · 2026Review
- EML4-ALK Variant-Specific Genetic Interactions Shape Lung Tumorigenesis.Cancer discovery · 2026Article
- Lorlatinib-specific outcomes by timing of lorlatinib initiation in advanced ALK-positive non-small cell lung cancer: A retrospective cohort study.Therapeutic advances in medical oncology · 2026Article
- Review
- Molecular Mechanisms and Treatment Strategies of ALK-Positive Lung Cancer: A Beginner's Guide for Patients, Their Families and Carers.Thoracic cancer · 2025Review
- APE1 Attenuates ALK Tyrosine Kinase Inhibitors Sensitivity in NPM1-ALK Positive Anaplastic Large Cell Lymphoma.Cancer science · 2025Article
- MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.Molecular oncology · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
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21 authors at 4 institutions in 1 country.
Funding
Abstract
Lorlatinib is currently the most advanced, potent and selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for the treatment of ALK-positive non-small cell lung cancer in the clinic; however, diverse compound ALK mutations driving therapy resistance emerge. Here, we determine the spectrum of lorlatinib-resistant compound ALK mutations in patients, following treatment with lorlatinib, the majority of which involve ALK G1202R or I1171N/S/T. We further identify structurally diverse lorlatinib analogs that harbor differential selective profiles against G1202R versus I1171N/S/T compound ALK mutations. Structural analysis revealed increased potency against compound mutations through improved inhibition of either G1202R or I1171N/S/T mutant kinases. Overall, we propose a classification of heterogenous ALK compound mutations enabling the development of distinct therapeutic strategies for precision targeting following sequential tyrosine kinase inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.