ArticleCancer discovery2016
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07045610 (Explore the Primary Resistance Mechanisms of Anaplastic Lymphoma Kinase Inhibitors), which is not on this map. Cited by 663 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Explore the Primary Resistance Mechanisms of Anaplastic Lymphoma Kinase Inhibitors
Who cites it
663 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,131 citations in OpenAlex.
- Background and clinical significance of biomarker-based patient enrichment in non-small-cell lung cancer drug development.Scientific reports · 2024Pooled it
- Lorlatinib in patients withFuture oncology (London, England) · 2026Trial
- Alectinib in combination with bevacizumab as first-line treatment in ALK-rearranged non-small cell lung cancer (ALEK-B): a single-arm, phase 2 trial.Nature communications · 2025Trial
- NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.Cancer discovery · 2024Trial
- Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study.Cancer communications (London, England) · 2024Trial
- Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial.Signal transduction and targeted therapy · 2023Trial
- Clinical characteristics of ALK-positive NSCLC patients treated with sequential ALK-TKI therapies in a single-centre.Lung cancer management · 2026Article
- Real-world evolution of first-line ALK-positive NSCLC management in Spain.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK-positive metastatic non-small cell lung cancer: A case report.Oncology letters · 2026Article
- Envonalkib Versus Crizotinib in Treatment-NaiveMedComm · 2026Article
- Review
- Review
- Monitoring EML4-ALK Biomarkers via a Microfluidic Assay for Treatment Efficacy Assessment.Biosensors · 2026Article
- Clinical utility of comprehensive genomic profiling in thoracic malignancies beyond conventional gene testing.International journal of clinical oncology · 2026Article
- First-Line Lorlatinib in Striatin-Anaplastic Lymphoma Kinase-Positive Lung Adenocarcinoma: A Case Report and Literature Review.Respirology case reports · 2026Article
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Current Research in Polypharmacology for Cancer Treatment Using Dual-Target Histone Deacetylase Inhibitors.International journal of molecular sciences · 2026Review
- Efficacy and safety of second-line treatments in ALK mutation-positive advanced non-small cell lung cancer after second- or third-generation ALK inhibitors: Turkish Oncology Group real-life study (TOG study).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Targeting non-small cell lung cancer: Molecular mechanisms and clinical studies (Review).Oncology letters · 2026Review
- Targeting MET in 2025: From Exon 14 Skipping to MET-Amplified Acquired Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Review
603 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 1 institution in 1 country.
Funding
Abstract
Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALK SIGNIFICANCE: Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. Cancer Discov; 6(10); 1118-33. ©2016 AACRSee related commentary by Qiao and Lovly, p. 1084This article is highlighted in the In This Issue feature, p. 1069.
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Registered trials
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.