Evidence map›Paper›PMID 26526352›Full record

ArticleJournal of experimental & clinical cancer research : CR2015

EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance.

Florian Sevelda, Lisa Mayr, Bernd Kubista, Daniela Lötsch, Sushilla van Schoonhoven, Reinhard Windhager, Christine Pirker, Michael Micksche, Walter Berger

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 10% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Application and mechanisms of targeting BRD4 in osteosarcoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Synthesis of Ursolic Acid-based Hybrids:Recent advances in anti-infective drug discovery · 2024
    Article
  14. Article
  15. Targeted therapy for osteosarcoma: a review.Journal of cancer research and clinical oncology · 2023
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
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

9 authors at 2 institutions in 1 country.

Florian SeveldaDepartment of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. florian.sevelda@meduniwien.ac.at.
Lisa MayrInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. lisa.mayr@meduniwien.ac.at.
Bernd KubistaDepartment of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. bernd.kubista@meduniwien.ac.at.
Daniela LötschInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. daniela.loetsch@meduniwien.ac.at.
Sushilla van SchoonhovenInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. sushilla.vanschoonhoven@meduniwien.ac.at.
Reinhard WindhagerDepartment of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. reinhard.windhager@meduniwien.ac.at.
Christine PirkerInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. christine.pirker@meduniwien.ac.at.
Michael MickscheInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. michael.micksche@meduniwien.ac.at.
Walter BergerInstitute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria. walter.berger@meduniwien.ac.at.
Comprehensive Cancer Center Vienna · ATMedical University of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEnhanced signalling via the epidermal growth factor receptor (EGFR) is a hallmark of multiple human carcinomas. However, in recent years data have accumulated that EGFR might also be hyperactivated in human sarcomas. Aim of this study was to investigate the influence of EGFR inhibition on cell viability and its interaction with chemotherapy response in osteosarcoma cell lines.

methodsWe have investigated a panel of human osteosarcoma cell lines regarding EGFR expression and downstream signalling. To test its potential applicability as therapeutic target, inhibition of EGFR by gefitinib was combined with osteosarcoma chemotherapeutics and cell viability, migration, and cell death assays were performed.

resultsOsteosarcoma cells expressed distinctly differing levels of functional EGFR reaching in some cases high amounts. Functionality of EGFR in osteosarcoma cells was proven by EGF-mediated activation of both MAPK and PI3K/AKT pathway (determined by phosphorylation of ERK1/2, AKT, S6, and GSK3β). The EGFR-specific inhibitor gefitinib blocked EGF-mediated downstream signal activation. At standard in vitro culture conditions, clinically achievable gefitinib doses demonstrated only limited cytotoxic activity, however, significantly reduced long-term colony formation and cell migration. In contrast, under serum-starvation conditions active gefitinib doses were distinctly reduced while EGF promoted starvation survival. Importantly, gefitinib significantly supported the anti-osteosarcoma activities of doxorubicin and methotrexate regarding cell survival and migratory potential.

conclusionOur data suggest that EGFR is not a major driver for osteosarcoma cell growth but contributes to starvation- and chemotherapy-induced stress survival. Consequently, combination approaches including EGFR inhibitors should be evaluated for treatment of high-grade osteosarcoma patients.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsApoptosisBone NeoplasmsCell CycleCell Line, TumorCell MovementCell ProliferationCell SurvivalErbB ReceptorsGefitinibGene ExpressionHumansOsteosarcomaPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsAntineoplastic AgentsErbB ReceptorsGefitinibPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktQuinazolines

Identifiers

PMID26526352
PMCPMC4630894
OpenAlexW2145369004

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.