Evidence map›Paper›PMID 31215502›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Afatinib and Temozolomide combination inhibits tumorigenesis by targeting EGFRvIII-cMet signaling in glioblastoma cells.

Raghupathy Vengoji, Muzafar A Macha, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Jawed A Siddiqui, Kavita Mallya, Santhi Gorantla, Maneesh Jain, Moorthy P Ponnusamy, Surinder K Batra and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.

  1. Pooled it
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  13. PUMA mediated afatinib-induced apoptosis in glioma cells.Archives of medical science : AMS · 2025
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25 more citing papers are in PubMed but not listed here.

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.

Raghupathy VengojiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Muzafar A MachaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Rama Krishna NimmakayalaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Jawed A SiddiquiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Kavita MallyaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Santhi GorantlaDepartment of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Maneesh JainDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. sbatra@unmc.edu.
Nicole ShonkaFred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA. nshonka@unmc.edu.
University of Nebraska Medical Center · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Joann B. Sweasy · 1985 to 2026
$55.0M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2018 to 2022
$8.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
MIC-1 and its functional partners in prostate cancer racial disparityU01CA185148 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2015 to 2019
$1.6M
Targeting Mucin and EGFR Axis in Pancreatic CancerR01CA183459 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2014 to 2018
$1.6M
Foundation for the National Institutes of Health U01185148NCI NIH HHS P01 CA217798NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA183459NCI NIH HHS R01 CA210637NCI NIH HHS U01 CA185148
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo.

methodsWe analyzed the effect of afatinib and temozolomide (TMZ) combination on GBM cells U87MG and U251 engineered to express wild type (WT) EGFR, EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts.

resultsAfatinib and TMZ combination synergistically inhibited the proliferation, clonogenic survival, motility, invasion and induced senescence of GBM cells compared to monotherapy. Mechanistically, afatinib decreased U87EGFRvIII GBM cell proliferation and motility/invasion by inhibiting EGFRvIII/AKT, EGFRvIII/JAK2/STAT3, and focal adhesion kinase (FAK) signaling pathways respectively. Interestingly, afatinib specifically inhibited EGFRvIII-cMET crosstalk in CSCs, resulting in decreased expression of Nanog and Oct3/4, and in combination with TMZ significantly decreased their self-renewal property in vitro. More interestingly, afatinib and TMZ combination significantly decreased the xenograft growth and progression compared to single drug alone.

conclusionOur study demonstrated significant inhibition of GBM tumorigenicity, CSC maintenance in vitro, and delayed tumor growth and progression in vivo by combination of afatinib and TMZ. Our results warrant evaluation of this drug combination in EGFR and EGFRvIII amplified GBM patients.

Indexed as

AfatinibAnimalsAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsCell Line, TumorCell ProliferationCell SurvivalErbB ReceptorsGene Expression Regulation, NeoplasticGlioblastomaHumansMiceNeoplastic Stem CellsProto-Oncogene Proteins c-metSignal TransductionTemozolomideAfatinibepidermal growth factor receptor VIIIErbB ReceptorsMET protein, humanProto-Oncogene Proteins c-metTemozolomideAfatinibCancer stem cellsEpidermal growth factor receptorGlioblastomaTemozolomide

Identifiers

PMID31215502
PMCPMC6582495
OpenAlexW2949310347

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LicenceCC BY
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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.