ReviewNature reviews. Clinical oncology2022
Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management.
Review in Nature reviews. Clinical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 333 papers, 4 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
333 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Advances in Aptamer Diagnostics Targeting Non-Small-Cell Lung Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors inBMJ (Clinical research ed.) · 2025Pooled it
- Pretreatment CT Texture Analysis for Predicting Survival Outcomes in Advanced Nonsmall Cell Lung Cancer Patients Receiving Immunotherapy: A Systematic Review and Meta-Analysis.Thoracic cancer · 2025Pooled it
- Cost-effectiveness analyses of amivantamab plus lazertinib and lazertinib versus osimertinib in non-small cell lung cancer with EGFR mutations.Frontiers in pharmacology · 2025Pooled it
- Sacituzumab tirumotecan versus docetaxel for previously treatedBMJ (Clinical research ed.) · 2025Trial
- Aumolertinib plus chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R: a phase II trial.The oncologist · 2025Trial
- Integrating clinical outcomes with molecular simulations to guide the selection of non-classical EGFR-TKIs: A comprehensive analysis and development of treatment strategies.Experimental and therapeutic medicine · 2026Article
- Envonalkib Versus Crizotinib in Treatment-NaiveMedComm · 2026Article
- Clinical Outcomes Associated with Single STK11 Mutations and Those Co-occurring with KEAP1 and KRAS Mutations in Metastatic Non-Small Cell Lung Cancer.Advances in therapy · 2026Article
- Retrospective real-world associations betweenTranslational lung cancer research · 2026Article
- Efficacy and safety of third-generationTranslational lung cancer research · 2026Article
- Treatment of an Advanced NSCLC Patient with a Rare OSBPL9-ALK Fusion: A Case Report.Healthcare (Basel, Switzerland) · 2026Article
- Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts.Cancer discovery · 2026Article
- A fungal-derived benzothiazole derivative overcomes osimertinib resistance in NSCLC by targeting SCD1.Natural products and bioprospecting · 2026Article
- Longitudinal spatial multi-omics delineates tumor microenvironment remodeling across sequential EGFR-TKIs in EGFR-mutant NSCLC.Journal of translational medicine · 2026Article
- Discovery of Potent EGFR Inhibitors for Del19 and L858R/T790M Mutants Through Structure-Based Virtual Screening and Biological Evaluation.Chemical biology & drug design · 2026Article
- A nomogram prediction model for brain metastases in patients with lung adenocarcinoma.Oncology letters · 2026Article
- Review
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- Multiclass Machine Learning-Based Discovery of Novel Scaffold Inhibitors Targeting ALK.Pharmaceuticals (Basel, Switzerland) · 2026Article
273 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors.
Funding
Abstract
The discoveries of EGFR mutations and ALK rearrangements as actionable oncogenic drivers in non-small-cell lung cancer (NSCLC) has propelled a biomarker-directed treatment paradigm for patients with advanced-stage disease. Numerous EGFR and ALK tyrosine kinase inhibitors (TKIs) with demonstrated efficacy in patients with EGFR-mutant and ALK-rearranged NSCLCs have been developed, culminating in the availability of the highly effective third-generation TKIs osimertinib and lorlatinib, respectively. Despite their marked efficacy, resistance to these agents remains an unsolved fundamental challenge. Both 'on-target' mechanisms (largely mediated by acquired resistance mutations in the kinase domains of EGFR or ALK) and 'off-target' mechanisms of resistance (mediated by non-target kinase alterations such as bypass signalling activation or phenotypic transformation) have been identified in patients with disease progression on osimertinib or lorlatinib. A growing understanding of the biology and spectrum of these mechanisms of resistance has already begun to inform the development of more effective therapeutic strategies. In this Review, we discuss the development of third-generation EGFR and ALK inhibitors, predominant mechanisms of resistance, and approaches to tackling resistance in the clinic, ranging from novel fourth-generation TKIs to combination regimens and other investigational therapies.
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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.