Evidence map›Paper›PMID 36428573›Full record

ArticleCancers2022

Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects.

Sebastian Gulde, Alessia Foscarini, Simon L April-Monn, Edoardo Genio, Alessandro Marangelo, Swapna Satam, Daniel Helbling, Massimo Falconi, Rodrigo A Toledo, Jörg Schrader and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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

13 authors at 5 institutions in 4 countries.

Sebastian GuldeInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.ORCID 0000-0002-8672-010X
Alessia FoscariniInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Simon L April-MonnInstitute of Pathology, University of Bern, 3012 Bern, Switzerland.ORCID 0000-0002-8941-7990
Edoardo GenioInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Alessandro MarangeloInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Swapna SatamInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Daniel HelblingOnkoZentrum Zurich, 8038 Zurich, Switzerland.
Massimo FalconiPancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.ORCID 0000-0001-9654-7243
Rodrigo A ToledoCIBERONC, Gastrointestinal and Endocrine Tumors, VHIO, 08035 Barcelona, Spain.
Jörg SchraderDepartment of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Aurel PerrenInstitute of Pathology, University of Bern, 3012 Bern, Switzerland.ORCID 0000-0002-6819-6092
Ilaria MarinoniInstitute of Pathology, University of Bern, 3012 Bern, Switzerland.
Natalia S PellegataInstitute for Diabetes and Cancer, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Heidelberg University · DEUniversity of Bern · CHCentro de Investigación Biomédica en Red de Cáncer · ESUniversität Hamburg · DEVita-Salute San Raffaele University · IT

Funding

Deutsche Forschungsgemeinschaft 314061271-TRR 205-B11German Cancer Aid 70113629Swiss Cancer Research Foundation KFS-4227-08-2017Wilhelm Sander Stiftung 2017.073.2 and 2017.012.1
6 · The paper itself

Abstract

Pancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (

Indexed as

buparlisibcombination therapypancreatic NETsprimary human tumoroidsribociclib

Identifiers

PMID36428573
PMCPMC9688197
OpenAlexW4308527953

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.