Evidence map›Paper›PMID 25587191›Full record

ArticleScience signaling2015

Annotation of human cancers with EGFR signaling-associated protein complexes using proximity ligation assays.

Matthew A Smith, Richard Hall, Kate Fisher, Scott M Haake, Farah Khalil, Matthew B Schabath, Vincent Vuaroqueaux, Heinz-Herbert Fiebig, Soner Altiok, Yian Ann Chen and 1 more

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

26 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. In Situ RAS:RAF Binding Correlates with Response to KRASG12C Inhibitors in KRASG12C-Mutant Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  3. Article
  4. Article
  5. Cell Type-specific Adaptive Signaling Responses to KRASClinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  6. Article
  7. Article
  8. Article
  9. Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2018
    Article
  10. Article
  11. Article
  12. MET-GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry-Based Phosphotyrosine Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016
    Article
  17. EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016
    Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Matthew A SmithDepartment of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Richard HallGraduate Medical Education, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Kate FisherDepartment of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Scott M HaakeGraduate Medical Education, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Farah KhalilDepartment of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Vincent VuaroqueauxOncotest GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
Heinz-Herbert FiebigOncotest GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
Soner AltiokDepartment of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Yian Ann ChenDepartment of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Eric B HauraDepartment of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. eric.haura@moffitt.org.
Moffitt Cancer Center · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
SPORE in Lung CancerP50CA119997 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI GABRILOVICH, DMITRY I · 2008 to 2012
$11.0M
Integrative Molecular Epidemiology WorkshopR25CA174664 · NCI · AMERICAN ASSOCIATION FOR CANCER RESEARCH · PI Shelley S Tworoger · 2013 to 2026
$2.8M
PROTEIN PROTEIN INTERACTIONS AS BIOMARKERSR21CA162178 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI HAURA, ERIC B. · 2011 to 2012
$400k
NCI NIH HHS P30 CA076292NCI NIH HHS P30-CA076292NCI NIH HHS P50 CA119997NCI NIH HHS P50-CA119997NCI NIH HHS R21 CA162178NCI NIH HHS R25 CA174664
6 · The paper itself

Abstract

Strategies to measure functional signaling-associated protein complexes have the potential to augment current molecular biomarker assays, such as genotyping and expression profiling, used to annotate diseases. Aberrant activation of epidermal growth factor receptor (EGFR) signaling contributes to diverse cancers. We used a proximity ligation assay (PLA) to detect EGFR in a complex with growth factor receptor-bound protein 2 (GRB2), the major signaling adaptor for EGFR. We used multiple lung cancer cell lines to develop and characterize EGFR:GRB2 PLA and correlated this assay with established biochemical measures of EGFR signaling. In a panel of patient-derived xenografts in mice, the intensity of EGFR:GRB2 PLA correlated with the reduction in tumor size in response to the EGFR inhibitor cetuximab. In tumor biopsies from three cohorts of lung cancer patients, positive EGFR:GRB2 PLA was observed in patients with and without EGFR mutations, and the intensity of EGFR:GRB2 PLA was predictive of overall survival in an EGFR inhibitor-treated cohort. Thus, we established the feasibility of using PLA to measure EGFR signaling-associated protein complexes in patient-based materials, suggesting the potential for similar assays for a broader array of receptor tyrosine kinases and other key signaling molecules.

Indexed as

AnimalsAntibodies, Monoclonal, HumanizedBiomarkers, TumorCell Line, TumorCetuximabErbB ReceptorsGRB2 Adaptor ProteinHeterograftsHumansImmunoassayLung NeoplasmsMiceMultiprotein ComplexesProtein Interaction MappingSignal TransductionAntibodies, Monoclonal, HumanizedBiomarkers, TumorCetuximabErbB ReceptorsGRB2 Adaptor ProteinMultiprotein Complexes

Identifiers

PMID25587191
PMCPMC4440040
OpenAlexW2025188134

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.