Evidence map›Paper›PMID 25173427›Full record

ArticleNature medicine2014

Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.

Christine M Lovly, Nerina T McDonald, Heidi Chen, Sandra Ortiz-Cuaran, Lukas C Heukamp, Yingjun Yan, Alexandra Florin, Luka Ozretić, Diana Lim, Lu Wang and 29 more

Expression of concernOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 178 papers.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed
27.8field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

178 citing papers in PubMed, 266 citations in OpenAlex.

  1. A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
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  3. Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
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118 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

39 authors at 10 institutions in 3 countries.

Christine M LovlyDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Nerina T McDonaldDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Heidi ChenDepartment of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
Sandra Ortiz-CuaranDepartment of Translational Genomics, Center of Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Lukas C Heukamp1] Department of Pathology, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany. [2] New Oncology, Cologne, Germany.
Yingjun YanDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Alexandra FlorinDepartment of Pathology, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Luka OzretićDepartment of Pathology, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Diana LimDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Lu WangDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Zhao ChenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Xi ChenDepartment of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
Pengcheng LuDepartment of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
Paul K PaikDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ronglai ShenDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Hailing JinDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Reinhard BuettnerDepartment of Pathology, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Sascha AnsénDepartment of Internal Medicine (Department I), Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Sven PernerDepartment of Prostate Cancer Research, Institute of Pathology, Center of Integrated Oncology Köln-Bonn, University Hospital of Bonn, Bonn, Germany.
Michael BrockmannDepartment of Pathology, Hospital Merheim, Cologne, Germany.
Marc Bos1] Department of Translational Genomics, Center of Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany. [2] Department of Internal Medicine (Department I), Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Jürgen WolfDepartment of Internal Medicine (Department I), Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Masyar GardiziDepartment of Internal Medicine (Department I), Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Gavin M WrightDepartment of Surgery, University of Melbourne, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Benjamin SolomonDivision of Hematology and Medical Oncology, Peter MacCallum Cancer Center, Melbourne, Australia.
Prudence A RussellDepartment of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Toni-Maree RogersDepartment of Pathology, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
Yoshiyuki SueharaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Monica Red-BrewerDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Rudy TieuAnti-tumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Elisa de StanchinaAnti-tumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Qingguo WangDepartment of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.
Zhongming ZhaoDepartment of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.ORCID 0000000234770914
David H JohnsonDepartment of Medicine, UT Southwestern School of Medicine, Dallas, Texas, USA.
Leora HornDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Kwok-Kin WongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Roman K Thomas1] Department of Translational Genomics, Center of Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany. [2] Department of Pathology, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
Marc LadanyiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
William PaoDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Vanderbilt University · USMemorial Sloan Kettering Cancer Center · USUniversity Hospital Cologne · DEIntegrated Oncology (United States) · USDana-Farber Cancer Institute · USPeter MacCallum Cancer Centre · AUBaylor School · USLungenklinik Köln-Merheim · DESt Vincent's Hospital Melbourne · AUThe University of Melbourne · AU

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
The Role of Focal Oncogene Amplifications in Lung CancerP01CA129243 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Andrea Ventura · 2007 to 2026
$31.2M
TARGETING NOTCH 3 IN LUNG CANCERP50CA090949 · NCI · VANDERBILT UNIVERSITY · PI MASSION, PIERRE P. · 2001 to 2011
$24.1M
StructureP01CA154303 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2012 to 2021
$17.8M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3M
Therapeutic strategies for specific subsets of KRAS mutant lung cancersR01CA140594 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WONG, KWOK KIN · 2009 to 2017
$4.5M
Overcoming acquired resistance to EGFR inhibitors in lung cancerR01CA121210 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LOVLY, CHRISTINE M. · 2007 to 2016
$2.9M
In vivo analysis of EGFR mutant driven lung cancers responses to radiation therapR01CA122794 · NCI · DANA-FARBER CANCER INST · PI WONG, KWOK KIN · 2006 to 2015
$2.8M
In vivo murine models of metastasis for therapeutic testingR01CA163896 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHARPLESS, NORMAN E, WONG, KWOK KIN · 2012 to 2016
$2.0M
Mapping the Genetic Architecture of Complex Disease via RNA-seq and GWAS DataR01LM011177 · NLM · VANDERBILT UNIVERSITY · PI WANG, LILY, ZHAO, ZHONGMING · 2012 to 2014
$1.0M
NCI NIH HHS CA122794NCI NIH HHS CA140594NCI NIH HHS CA154303NCI NIH HHS CA163896NCI NIH HHS CA166480NCI NIH HHS CA90949NCI NIH HHS K12 CA090625NCI NIH HHS K12 CA9060625NCI NIH HHS P01 CA129243NCI NIH HHS P01CA129243NCI NIH HHS P01 CA154303NCI NIH HHS P30 CA068485NCI NIH HHS P30-CA68485NCI NIH HHS P50 CA090949NCI NIH HHS R01 CA121210NCI NIH HHS R01CA121210NCI NIH HHS R01 CA122794NCI NIH HHS R01 CA140594NCI NIH HHS R01 CA163896NCI NIH HHS R01 CA166480NLM NIH HHS R01 LM011177NLM NIH HHS R01LM011177
6 · The paper itself

Abstract

Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the clinical observation of a patient with ALK fusion-positive lung cancer who had an exceptional response to an insulin-like growth factor 1 receptor (IGF-1R)-specific antibody, we define a therapeutic synergism between ALK and IGF-1R inhibitors. Similar to IGF-1R, ALK fusion proteins bind to the adaptor insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effects of ALK inhibitors. In models of ALK TKI resistance, the IGF-1R pathway is activated, and combined ALK and IGF-1R inhibition improves therapeutic efficacy. Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy. Collectively these data support a role for the IGF-1R-IRS-1 pathway in both ALK TKI-sensitive and ALK TKI-resistant states and provide a biological rationale for further clinical development of dual ALK and IGF-1R inhibitors.

Indexed as

Anaplastic Lymphoma KinaseCrizotinibFemaleGene Knockdown TechniquesHumansInsulin Receptor Substrate ProteinsLung NeoplasmsMiddle AgedPyrazolesPyridinesReceptor, IGF Type 1Receptor Protein-Tyrosine KinasesUp-RegulationALK protein, humanAnaplastic Lymphoma KinaseCrizotinibInsulin Receptor Substrate ProteinsIRS1 protein, humanPyrazolesPyridinesReceptor, IGF Type 1Receptor Protein-Tyrosine Kinases

Identifiers

PMID25173427
PMCPMC4159407
OpenAlexW2082020673

What OpenQuestion holds

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Registered trials

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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.