ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Co-clinical FDG-PET radiomic signature in predicting response to neoadjuvant chemotherapy in triple-negative breast cancer.European journal of nuclear medicine and molecular imaging · 2022Trial
- Crizotinib attenuates bleomycin-induced pulmonary fibrosis via regulating fibroblast activation.Journal of thoracic disease · 2026Article
- The Expression and Molecular Roles of MAMDC2 in MSS Colorectal Cancer with a High Tumor Stromal Ratio.Biomedicines · 2025Article
- Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer-A Validation Study.International journal of molecular sciences · 2024Article
- EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.The Journal of experimental medicine · 2024Article
- A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.Acta pharmaceutica Sinica. B · 2024Article
- miRNA-Seq Tissue Diagnostic Signature: A Novel Model for NSCLC Subtyping.International journal of molecular sciences · 2023Article
- Harnessing preclinical models for the interrogation of ovarian cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC.EMBO molecular medicine · 2022Article
- Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development.Cold Spring Harbor perspectives in medicine · 2021Review
- Exploring liver cancer biology through functional genetic screens.Nature reviews. Gastroenterology & hepatology · 2021Review
- Article
- Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine.Tomography (Ann Arbor, Mich.) · 2020Article
- Preclinical PERCIST and 25% of SUVJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Epigenetics and cell cycle regulation in cystogenesis.Cellular signalling · 2020Review
- Preclinical Metrics Correlate With Drug Activity in Phase II Trials of Targeted Therapies for Non-Small Cell Lung Cancer.Frontiers in oncology · 2020Article
- Current and Future Horizons of Patient-Derived Xenograft Models in Colorectal Cancer Translational Research.Cancers · 2019Review
- Patient-derived xenograft mouse models: A high fidelity tool for individualized medicine.Oncology letters · 2019Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
purposeTo extend the results of a phase III trial in patients with non-small cell lung cancer with adenocarcinomas harboring EML4-ALK fusion. EXPERIMENTAL
designWe conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed.
resultsConcordant with the clinical outcome in humans, crizotinib produced a substantially higher response rate compared with chemotherapy, associated with significantly longer progression-free survival. Overall survival was also prolonged in crizotinib- compared with chemotherapy-treated mice. Pemetrexed produced superior overall survival compared with docetaxel, suggesting that this agent may be the preferred chemotherapy in the ALK population. In addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance. Furthermore, HSP90 inhibition, as well as the second-generation ALK inhibitor TAE684, demonstrated activity in newly developed lung adenocarcinoma models driven by crizotinib-insensitive EML4-ALK L1196M or F1174L.
conclusionsOur findings suggest that crizotinib is superior to standard chemotherapy in ALK inhibitor-naïve disease and support further clinical investigation of HSP90 inhibitors and second-generation ALK inhibitors in tumors with primary or acquired crizotinib resistance.
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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.