Evidence map›Paper›PMID 35224804›Full record

ArticleHead & neck2022

Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.

Nicole L Michmerhuizen, Megan L Ludwig, Andrew C Birkeland, Sai Nimmagadda, Jingyi Zhai, Jiayu Wang, Brittany M Jewell, Dylan Genouw, Lindsay Remer, Daniel Kim and 8 more

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

Article in Head & neck, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
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

18 authors at 1 institution in 1 country.

Nicole L MichmerhuizenDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Megan L LudwigDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Andrew C BirkelandDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Sai NimmagaddaDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Jingyi ZhaiDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Jiayu WangDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Brittany M JewellDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Dylan GenouwDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Lindsay RemerDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Daniel KimDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Susan K FoltinDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Apurva BhangaleDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Aditi KulkarniDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Carol R BradfordDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Paul L SwiecickiDepartment of Hematology and Oncology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Thomas E CareyDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Hui JiangDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
J Chad BrennerDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.ORCID 0000-0003-3238-1111
University of Michigan · US

Funding

Dissecting Co-Dependent Pathways in Oral CancersU01DE025184 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BRENNER, JOHN CHADWICK, CAREY, THOMAS E. · 2015 to 2018
$3.7M
Molecular Mechanisms of Tumor Behavior and Response to Therapy in HPV-positive Oropharyngeal CancerR01CA194536 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CAREY, THOMAS E. · 2016 to 2021
$2.8M
Investigating the Mechanisms of Resistance to EGFR-Targeted Therapy in Head and Neck Squamous Cell CarcinomaF31CA206341 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUDWIG, MEGAN LOREE · 2017 to 2019
$93k
NCI NIH HHS F31 CA206341NCI NIH HHS R01 CA194536NIDCR NIH HHS U01 DE025184
6 · The paper itself

Abstract

backgroundHead and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival. Although epidermal growth factor receptor (EGFR)-targeting antibody cetuximab improves survival in some settings, responses are limited suggesting that alternative approaches are needed.

methodsWe performed a high throughput drug screen to identify EGFR inhibitor-based synergistic combinations of clinically advanced inhibitors in models resistant to EGFR inhibitor monotherapies, and then performed downstream validation experiments on prioritized synergistic combinations.

resultsFrom our screen, we re-discovered known synergistic EGFR inhibitor combinations with FGFR or IGF-1R inhibitors that were broadly effective and also discovered novel synergistic combinations with XIAP inhibitor and DNMT inhibitors that were effective in only a subset of models.

conclusionsConceptually, our data identify novel synergistic combinations that warrant evaluation in future studies, and suggest that some combinations, although highly synergistic, will require parallel companion diagnostic development to be effectively advanced in patients.

Indexed as

Antineoplastic AgentsHead and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckCell Line, TumorCetuximabErbB ReceptorsHumansProtein Kinase InhibitorsAntineoplastic AgentsCetuximabEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID35224804
PMCPMC8986607
OpenAlexW4214487221

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.