Evidence map›Paper›PMID 24986420›Full record

ArticleHead & neck2015

Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways.

Mark J Axelrod, Rolando E Mendez, Ashraf Khalil, Stephanie S Leimgruber, Elizabeth R Sharlow, Brian Capaldo, Mark Conaway, Daniel G Gioeli, Michael J Weber, Mark J Jameson

Open access · greenAbstract read
In one paragraph

Article in Head & neck, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

10 authors at 2 institutions in 2 countries.

Mark J AxelrodDepartment of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.
Rolando E MendezDepartment of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.
Ashraf KhalilDepartment of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.
Stephanie S LeimgruberDepartment of Pharmacology, University of Virginia Health System, Charlottesville, Virginia.
Elizabeth R SharlowDepartment of Pharmacology, University of Virginia Health System, Charlottesville, Virginia.
Brian CapaldoDepartment of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia.
Mark ConawayDepartment of Health Evaluation Sciences, University of Virginia Health System, Charlottesville, Virginia.
Daniel G GioeliDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia.
Michael J WeberDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia.
Mark J JamesonDepartment of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.
University of Virginia Health System · USMenoufia University · EG

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Thomas P. Loughran · 1987 to 2026
$72.1M
Neuroendocrine Cell Signaling in Prostate CancerP01CA076465 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI WEBER, MICHAEL J · 1999 to 2003
$3.6M
Checkpoint Signaling and Androgen Receptor Function in Prostate CancerR01CA178338 · NCI · UNIVERSITY OF VIRGINIA · PI GIOELI, DANIEL G · 2014 to 2018
$1.6M
Growth Factor-Induced Resistance to Targeted Therapy in Oral Cavity CancerK08DE019477 · NIDCR · UNIVERSITY OF VIRGINIA · PI JAMESON, MARK J · 2009 to 2013
$540k
NCI NIH HHS P01 CA076465NCI NIH HHS P30 CA044579NCI NIH HHS P30-CA044579NCI NIH HHS R01 CA178338NIDCR NIH HHS K08 DE019477NIDCR NIH HHS K08-DE019477
6 · The paper itself

Abstract

backgroundIn head and neck squamous cell carcinoma (HNSCC), resistance to single-agent targeted therapy may be overcome by co-targeting of compensatory signaling pathways.

methodsA targeted drug screen with 120 combinations was used on 9 HNSCC cell lines.

resultsMultiple novel drug combinations demonstrated synergistic growth inhibition. Combining the insulin-like growth factor-1 receptor (IGF-1R) inhibitor, BMS754807, with either the human epidermal growth factor receptor (HER)-family inhibitor, BMS599626, or the Src-family kinase inhibitor, dasatinib, resulted in substantial synergy and growth inhibition. Depending on the cell line, these combinations induced synergistic or additive apoptosis; when synergistic apoptosis was observed, AKT phosphorylation was inhibited to a greater extent than either drug alone. Conversely, when additive apoptosis occurred, AKT phosphorylation was not reduced by the drug combination.

conclusionCombined IGF-1R/HER family and IGF-1R/Src family inhibition may have therapeutic potential in HNSCC. AKT may be a node of convergence between IGF-1R signaling and pathways that compensate for IGF-1R inhibition.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsApoptosisCarbamatesCarcinoma, Squamous CellCell Culture TechniquesCell Line, TumorDasatinibDrug Resistance, NeoplasmDrug SynergismHead and Neck NeoplasmsHumansPhosphorylationProto-Oncogene Proteins c-aktPyrazolesReceptor, IGF Type 1Signal Transduction(4-((1-(3-fluorophenyl)methyl)-1H-indazol-5-ylamino)-5-methylpyrrolo(2,1-f)(1,2,4)triazin-6-yl)carbamic acid 3-morpholinylmethyl esterBMS 754807CarbamatesDasatinibProto-Oncogene Proteins c-aktPyrazolesReceptor, IGF Type 1Triazinescombination therapycompensatory signalingdrug resistancehead and neck squamous cell carcinomainsulin-like growth factor-1 receptor

Identifiers

PMID24986420
PMCPMC7376763
OpenAlexW1554356955

What OpenQuestion holds

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LicenceTDM
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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.