ArticleEMBO molecular medicine2022
A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies.Technology in cancer research & treatmentPooled it
- A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Genome biology · 2026Article
- Molecular Mechanisms and Treatment Strategies of ALK-Positive Lung Cancer: A Beginner's Guide for Patients, Their Families and Carers.Thoracic cancer · 2025Review
- Spectrum of Resistance Mechanisms to ALK TKIs in NSCLC: Largest Single-Center Experience from India.South Asian journal of cancer · 2025Article
- Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2025Review
- Synthesis and Antitumor Activity of 6-(2-Aminobenzo[ACS omega · 2025Article
- Article
- The synthesis and evaluation of novel ALK inhibitors containing the sulfoxide structure.RSC advances · 2024Article
- Apatinib plus chemotherapy is associated with an improved tumor response, survival and tolerance compared with chemotherapy alone for advanced lung adenocarcinoma treatment.Oncology letters · 2024Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- Neoadjuvant therapy for non-small cell lung cancer and esophageal cancer.American journal of cancer research · 2024Review
- Novel biomolecules in targeted cancer therapy: a new approach towards precision medicine.Medical oncology (Northwood, London, England) · 2023Review
- Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.Frontiers in pharmacology · 2023Review
- Biomarker-Targeted Therapies in Non-Small Cell Lung Cancer: Current Status and Perspectives.Cells · 2022Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC.EMBO molecular medicine · 2022Article
- Targeting ALK Rearrangements in NSCLC: Current State of the Art.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
29 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement. However, most patients inevitably develop crizotinib resistance due to acquired secondary mutations in the ALK kinase domain, such as the gatekeeper mutation L1196M and the most refractory mutation, G1202R. Here, we develop XMU-MP-5 as a new-generation ALK inhibitor to overcome crizotinib resistance mutations, including L1196M and G1202R. XMU-MP-5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild-type or mutant EML4-ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo. Structural analysis provides insights into the mode of action of XMU-MP-5. In addition, XMU-MP-5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models, further demonstrating its pharmacological efficacy and potential for clinical application. These preclinical data support XMU-MP-5 as a novel selective ALK inhibitor with high potency and selectivity. XMU-MP-5 holds great promise as a new therapeutic against clinically relevant secondary ALK mutations.
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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.