ReviewMolecular oncology2023
EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries.
Review in Molecular oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- A meta-analysis of the impact of different ALK variants on targeted therapy efficacy in advanced non-small cell lung cancer.Frontiers in oncology · 2026Pooled it
- EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies.Technology in cancer research & treatmentPooled it
- Observed ALK fusion/rearrangement frequency across comprehensive genomic profiling platforms in Japanese routine oncology practice.International journal of clinical oncology · 2026Article
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Exploring the Impact of Multiple Gene Mutations on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Response in Asian Nonsmall Cell Lung Cancer Patients.ACS pharmacology & translational science · 2026Review
- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3.Scientific reports · 2026Article
- Analysis of clinical features and outcomes in a Chinese cohort withFrontiers in oncology · 2026Article
- A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.Oncology research · 2026Review
- Safety recommendations for ALK tyrosine kinase inhibitors in non-small cell lung cancer: evidence from FAERS and CVARDD real-world databases.Frontiers in oncology · 2026Article
- Radiotherapy for large ruptured hemorrhagic axillary lymph node metastasis from anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report and review of literature.World journal of clinical oncology · 2025Article
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?Cancers · 2025Review
- Trimerization domain-interfering peptide inhibits EML4-ALK condensate formation, fusion-dependent signaling, and cell growth.Molecular biology of the cell · 2025Article
- APE1 Attenuates ALK Tyrosine Kinase Inhibitors Sensitivity in NPM1-ALK Positive Anaplastic Large Cell Lymphoma.Cancer science · 2025Article
- Machine Learning and Integrative Structural Dynamics Identify Potent ALK Inhibitors from Natural Compound Libraries.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with AdvancedInternational journal of molecular sciences · 2025Review
- Dual inhibition of GTP-bound KRAS and mTOR in lung adenocarcinoma and squamous cell carcinoma harboring KRAS G12C.Cell communication and signaling : CCS · 2025Article
- Synthesis and Antitumor Activity of 6-(2-Aminobenzo[ACS omega · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK) can be driven to oncogenic activity by different types of mutational events such as point-mutations, for example F1174L in neuroblastoma, and gene fusions, for example with echinoderm microtubule-associated protein-like 4 (EML4) in non-small cell lung cancer (NSCLC). EML4-ALK variants result from different breakpoints, generating fusions of different sizes and properties. The most common variants (Variant 1 and Variant 3) form cellular compartments with distinct physical properties. The presence of a partial, probably misfolded beta-propeller domain in variant 1 confers solid-like properties to the compartments it forms, greater dependence on Hsp90 for protein stability and higher cell sensitivity to ALK tyrosine kinase inhibitors (TKIs). These differences translate to the clinic because variant 3, on average, worsens patient prognosis and increases metastatic risk. Latest generation ALK-TKIs are beneficial for most patients with EML4-ALK fusions. However, resistance to ALK inhibitors can occur via point-mutations within the kinase domain of the EML4-ALK fusion, for example G1202R, reducing inhibitor effectiveness. Here, we discuss the biology of EML4-ALK variants, their impact on treatment response, ALK-TKI drug resistance mechanisms and potential combination therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.