Evidence map›Paper›PMID 27469115›Full record

ArticleCancer research2016

SMAC Mimetic Birinapant plus Radiation Eradicates Human Head and Neck Cancers with Genomic Amplifications of Cell Death Genes FADD and BIRC2.

Danielle F Eytan, Grace E Snow, Sophie Carlson, Adeeb Derakhshan, Anthony Saleh, Stephen Schiltz, Hui Cheng, Suresh Mohan, Shaleeka Cornelius, Jamie Coupar and 6 more

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

Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 12% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
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  15. FADD as a key molecular player in cancer progression.Molecular medicine (Cambridge, Mass.) · 2022
    Review
  16. Article
  17. Review
  18. Article
  19. BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021
    Review
  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

16 authors at 3 institutions in 1 country.

Danielle F Eytan *Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Grace E Snow *Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Sophie Carlson *Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Adeeb Derakhshan *Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Anthony Saleh *Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Stephen SchiltzTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Hui ChengTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Suresh MohanTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Shaleeka CorneliusTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Jamie CouparTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Anastasia L SowersRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Lidia HernandezWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
James B MitchellRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Christina M AnnunziataWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Zhong ChenTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Carter Van WaesTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
National Institute on Deafness and Other Communication Disorders · USFoundation for the National Institutes of Health · USNational Cancer Institute · US

Funding

Modulation of Therapeutic ResponseZIASC006321 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI MITCHELL, JAMES · 2009 to 2025
$17.3M
Genomics and Proteomics of Head and Neck CancerZIADC000074 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$11.1M
NF-kappaB in pathogenesis and therapy of head and neck cancerZIADC000016 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.3M
Signal and Transcription Factor Network interactions in Head and Neck CancerZIADC000073 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.1M
NF-kappaB in pathogenesis and therapy of head and neck cancerZ01DC000016 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 1994 to 2008
$2.9M
Intramural NIH HHS Z01 DC000016Intramural NIH HHS ZIA DC000016Intramural NIH HHS ZIA DC000073Intramural NIH HHS ZIA DC000074
6 · The paper itself

Abstract

Comparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporting their functional importance in promoting proliferation. Birinapant, a novel SMAC mimetic, sensitized multiple HNSCC lines to cell death by agonists TNFα or TRAIL and inhibited cIAP1>XIAP>IAP2. Combination of birinapant and TNFα induced sub-G0 DNA fragmentation in sensitive lines and birinapant alone also induced significant G2-M cell-cycle arrest and cell death in UM-SCC-46 cells. Gene transfer and expression of FADD sensitized resistant UM-SCC-38 cells lacking FADD amplification to birinapant and TNFα, supporting a role for FADD in sensitization to IAP inhibitor and death ligands. HNSCC varied in mechanisms of cell death, as indicated by reversal by inhibitors or protein markers of caspase-dependent apoptosis and/or RIPK1/MLKL-mediated necroptosis. In vivo, birinapant inhibited tumor growth and enhanced radiation-induced TNFα, tumor responses, and host survival in UM-SCC-46 and -11B xenograft models displaying amplification and overexpression of FADD+/- BIRC2 These findings suggest that combination of SMAC mimetics such as birinapant plus radiation may be particularly active in HNSCC, which harbor frequent FADD/BIRC2 genomic alterations. Cancer Res; 76(18); 5442-54. ©2016 AACR.

Indexed as

AnimalsAntineoplastic AgentsBlotting, WesternCarcinoma, Squamous CellCell Line, TumorChemoradiotherapyDipeptidesFas-Associated Death Domain ProteinFemaleGene AmplificationGene Knockdown TechniquesHead and Neck NeoplasmsHumansImmunohistochemistryIndolesInhibitor of Apoptosis ProteinsAntineoplastic AgentsBIRC2 protein, humanbirinapantDipeptidesFADD protein, humanFas-Associated Death Domain ProteinIndolesInhibitor of Apoptosis ProteinsTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaUbiquitin-Protein Ligases

Identifiers

PMID27469115
PMCPMC5026594
OpenAlexW2496353082

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.