Evidence map›Paper›PMID 29232766›Full record

ArticleCell proliferation2018

Combined Erlotinib and PF-03084014 treatment contributes to synthetic lethality in head and neck squamous cell carcinoma.

Yang Zheng, Zhao Wang, Xu Ding, Yibo Dong, Wei Zhang, Wei Zhang, Yi Zhong, Wenyi Gu, Yunong Wu, Xiaomeng Song

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

Article in Cell proliferation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

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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.

Yang ZhengKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Zhao WangKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Xu DingKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Yibo DongKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Wei ZhangKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Wei ZhangKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Yi ZhongKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Wenyi GuAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Qld., Australia.
Yunong WuKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.
Xiaomeng SongKey Laboratory of Oral Diseases of Jiangsu Province, Stomatological Institute of Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0001-7103-6359
Nanjing Medical University · CNThe University of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesHead and neck squamous cell carcinoma (HNSCC) is characterized by high mortality and low survival rates. As an epidermal growth factor receptor (EGFR) inhibitor, Erlotinib has been approved for treatment of various tumours. PF-03084014 is a selective inhibitor of Notch1 signalling. This study aimed to explore new approaches for simultaneously targeting EGFR and Notch1 signalling to attenuate tumour growth and improve survival. MATERIALS AND

methodsCell proliferation was determined by CCK-8 assay and Flow cytometry. Cell invasive ability was determined by Transwell assay. Western blot was used to test the expression of Notch1 and EGFR pathway. Cleaved Caspase-3 staining and TUNEL assay were used to verify the apoptosis through combined treatment.

resultsWe first confirmed proliferative inhibition and cell death in HNSCC with combined Erlotinib and PF-03084014 treatment. Moreover, we found PF-03084014 reversed the increased invasion induced by Erlotinib. In a preclinical therapeutic drug trial in vivo, combined treatment effectively abrogated tumour growth. Most importantly, one mechanism was found that PF-03084014 alone could activate the PI3K/AKT signalling, the downstream of EGFR signalling, and Erlotinib alone could activate the intracellular domain of Notch1 (NICD), while combined treatment of PF-03084014 and Erlotinib suppressed the HNSCC growth.

conclusionsThese results suggested that concomitant inhibition of the Notch1 and EGFR pathways represented a rational strategy for promoting apoptosis in HNSCC and overcoming treatment resistance.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCarcinoma, Squamous CellCell Line, TumorCell ProliferationDrug SynergismErlotinib HydrochlorideHead and Neck NeoplasmsHumansMaleMice, Inbred BALB CMice, NudeMolecular Targeted TherapyNeoplasm InvasivenessSignal TransductionErlotinib HydrochloridenirogacestatTetrahydronaphthalenesValineAKTErlotinibHNSCCNICDPF-03084014synthetic lethality

Identifiers

PMID29232766
PMCPMC6528911
OpenAlexW2774875421

What OpenQuestion holds

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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.