Evidence map›Paper›PMID 27283993›Full record

ArticleNature communications2016

Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients.

Jacob J Chabon, Andrew D Simmons, Alexander F Lovejoy, Mohammad S Esfahani, Aaron M Newman, Henry J Haringsma, David M Kurtz, Henning Stehr, Florian Scherer, Chris A Karlovich and 12 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2016. 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 367 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
367citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

367 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  5. Circulating Tumor DNA as a Biomarker in Patients With Stage III and IV Wilms Tumor: Analysis From a Children's Oncology Group Trial, AREN0533.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
    Trial
  6. Trial
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  8. Article
  9. Review
  10. Review
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  12. A Decadal Bibliometric Analysis of Circulating Tumor DNA (ctDNA) Research in Lung Cancer (2012-2022).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  13. Review
  14. Article
  15. Article
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  17. Article
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  20. Article

307 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Jacob J ChabonInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Andrew D SimmonsClovis Oncology, Inc., San Francisco, California 94158, USA.
Alexander F LovejoyInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Mohammad S EsfahaniInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Aaron M NewmanInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Henry J HaringsmaClovis Oncology, Inc., San Francisco, California 94158, USA.
David M KurtzDivision of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Henning StehrInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Florian SchererStanford Cancer Institute, Stanford University, Stanford, California 94305, USA.
Chris A KarlovichClovis Oncology, Inc., San Francisco, California 94158, USA.
Thomas C HardingClovis Oncology, Inc., San Francisco, California 94158, USA.
Kathleen A DurkinMolecular Graphics and Computation Facility, College of Chemistry, University of California, Berkeley, California 94720, USA.
Gregory A OttersonThe Ohio State University, Columbus, Ohio 43210, USA.
W Thomas PurcellDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
D Ross CamidgeDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Jonathan W GoldmanDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
Lecia V SequistMassachusetts General Hospital &Harvard Medical School, Boston, Massachusetts 02115, USA.
Zofia PiotrowskaMassachusetts General Hospital &Harvard Medical School, Boston, Massachusetts 02115, USA.
Heather A WakeleeDivision of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Joel W NealDivision of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Ash A AlizadehInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.ORCID 0000-0002-5153-5625
Maximilian DiehnInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.ORCID 0000-0003-2032-0581

Funding

Tissue Bank and Biomarkers CoreP50CA058187 · NCI · UNIVERSITY OF COLORADO DENVER · PI NEMENOFF, RAPHAEL A. · 1992 to 2018
$43.8M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Modeling the Molecular Determinants of Induced Anti-Tumor Immune Responses in Mantle Cell LymphomaU01CA194389 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DAVIS, MARK MORRIS · 2015 to 2019
$3.1M
Developing a genomic approach for cancer screeningDP2CA186569 · NCI · STANFORD UNIVERSITY · PI DIEHN, MAXIMILIAN · 2013 to 2013
$2.4M
Cancer Systems Biology Scholars ProgramR25CA180993 · NCI · STANFORD UNIVERSITY · PI PLEVRITIS, SYLVIA KATINA · 2014 to 2018
$2.2M
Postdoctoral Training in the Radiation ScincesT32CA121940 · NCI · STANFORD UNIVERSITY · PI GRAVES, EDWARD E. · 2007 to 2018
$2.1M
Noninvasive monitoring of lung cancer patients treated with radiotherapyR01CA188298 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2015 to 2019
$1.8M
NCI NIH HHS DP2 CA186569NCI NIH HHS P50 CA058187NCI NIH HHS R01 CA188298NCI NIH HHS R25 CA180993NCI NIH HHS T32 CA009302NCI NIH HHS T32 CA121940NCI NIH HHS U01 CA194389
6 · The paper itself

Abstract

Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment.

Indexed as

AcrylamidesCarcinoma, Non-Small-Cell LungCirculating Tumor DNACohort StudiesCrizotinibDrug Resistance, NeoplasmErbB ReceptorsGene AmplificationGene DosageGenetic HeterogeneityHumansLung NeoplasmsMutationProtein Kinase InhibitorsProto-Oncogene Proteins c-metPyrazolesAcrylamidesCirculating Tumor DNACrizotinibErbB ReceptorsProtein Kinase InhibitorsProto-Oncogene Proteins c-metPyrazolesPyridinesPyrimidinesrociletinib

Identifiers

PMID27283993
PMCPMC4906406

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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.