Evidence map›Paper›PMID 33809148›Full record

ArticleCancers2021

Preclinical Evaluation of the Association of the Cyclin-Dependent Kinase 4/6 Inhibitor, Ribociclib, and Cetuximab in Squamous Cell Carcinoma of the Head and Neck.

Gabrielle van Caloen, Sandra Schmitz, Cédric van Marcke, Xavier Caignet, Antonella Mendola, Sébastien Pyr Dit Ruys, Pierre P Roger, Didier Vertommen, Jean-Pascal Machiels

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 11 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

9 authors at 4 institutions in 1 country.

Gabrielle van CaloenInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.ORCID 0000-0001-6827-7215
Sandra SchmitzInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.ORCID 0000-0002-9943-2078
Cédric van MarckeInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.ORCID 0000-0003-3454-0630
Xavier CaignetInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.
Antonella MendolaInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.
Sébastien Pyr Dit RuysProtein Phosphorylation Unit, de Duve Institute, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 74, 1200 Brussels, Belgium.ORCID 0000-0002-5449-1541
Pierre P RogerCancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Didier VertommenProtein Phosphorylation Unit, de Duve Institute, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 74, 1200 Brussels, Belgium.ORCID 0000-0001-7648-8282
Jean-Pascal MachielsInstitut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 57, 1200 Brussels, Belgium.ORCID 0000-0001-6369-9742
Cliniques Universitaires Saint-Luc · BEUCLouvain · BEde Duve Institute · BEUniversité Libre de Bruxelles · BE

Funding

Fonds De La Recherche Scientifique - FNRS FRSM 2013Fonds De La Recherche Scientifique - FNRS Télévie/FNRS N22824344WALInove 2017-02 CICLIBTEST
6 · The paper itself

Abstract

Epidermal growth factor receptor (EGFR) overexpression is observed in 90% of human papillomavirus (HPV)-negative squamous cell carcinomas of the head and neck (SCCHN). Cell cycle pathway impairments resulting in cyclin-dependent kinase (CDK) 4 and 6 activation, are frequently observed in SCCHN. We investigated the efficacy of ribociclib, a CDK4/6 inhibitor, in combination with cetuximab, a monoclonal antibody targeting the EGFR, in HPV-negative SCCHN patient-derived tumor xenograft (PDTX) models. The combination of cetuximab and ribociclib was not significantly more active than cetuximab monotherapy in all models investigated. In addition, the combination of cetuximab and ribociclib was less active than ribociclib monotherapy in the cetuximab-resistant PDTX models. In these models, a significant downregulation of the retinoblastoma (Rb) protein was observed in cetuximab-treated mice. We also observed Rb downregulation in the SCCHN cell lines chronically exposed and resistant to cetuximab. In addition, Rb downregulation induced interleukin 6 (Il-6) secretion and the Janus kinase family member/signal transducer and activator of transcription (JAK/STAT) pathway activation that might be implicated in the cetuximab resistance of these cell lines. To conclude, cetuximab is not an appropriate partner for ribociclib in cetuximab-resistant SCCHN models. Our work has significant clinical implications since the combination of anti-EGFR therapy with CDK4/6 inhibitors is currently being investigated in clinical trials.

Indexed as

CDK4/6cetuximabresistanceretinoblastomaribociclibsquamous cell carcinoma of the head and neck

Identifiers

PMID33809148
PMCPMC7998503
OpenAlexW3136419000

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.