Evidence map›Paper›PMID 39217851›Full record

ArticleTranslational oncology2024

Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

Jingyu An, Roma Kurilov, Teresa Peccerella, Frank Bergmann, Mouad Edderkaoui, Adrian Lim, Xu Zhou, Katrin Pfütze, Angela Schulz, Stephan Wolf and 21 more

Abstract read
In one paragraph

Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. 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

31 authors.

Jingyu AnHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Roma KurilovDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Berliner Str. 41, Heidelberg 69120, Germany.
Teresa PeccerellaHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Frank BergmannInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Mouad EdderkaouiDepartment of Medicine, Cedars-Sinai Medical Center and University of California at Los Angeles, Thalians W204 8700 Beverly Blvd. Los Angeles, California CA 90048, United States.
Adrian LimDepartment of Medicine, Cedars-Sinai Medical Center and University of California at Los Angeles, Thalians W204 8700 Beverly Blvd. Los Angeles, California CA 90048, United States.
Xu ZhouHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Katrin PfützeSample Processing Laboratory, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
Angela SchulzNGS Core Facility, The German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stephan WolfNGS Core Facility, The German Cancer Research Center (DKFZ), Heidelberg, Germany.
Kai HuHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Christoph SpringfeldDepartment of Medical Oncology, National Center for Tumor Diseases, University Clinic Heidelberg, Heidelberg 69120, Germany.
Sadaf S MughalDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Berliner Str. 41, Heidelberg 69120, Germany.
Lenart ZezlinaDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Berliner Str. 41, Heidelberg 69120, Germany.
Franco FortunatoHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Georg BeyerDepartment of Internal Medicine II, Ludwig-Maximilians-University of Munich, Germany.
Julia MayerleDepartment of Internal Medicine II, Ludwig-Maximilians-University of Munich, Germany.
Susanne RothHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Johannes HulkkonenHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Daniela MerzHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Shigenori EiDepartment of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan.
Arianeb MehrabiHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Martin LoosHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Mohammed Al-SaeediHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Christoph W MichalskiHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany.
Markus W BüchlerHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany; Botton-Champalimaud Pancreatic Cancer Centre, Lisbon, Portugal.
Thilo HackertHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany; Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Benedikt BrorsDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Berliner Str. 41, Heidelberg 69120, Germany; German Cancer Consortium (DKTK), Core Center Heidelberg, Im Neuenheimer Feld 280, Heidelberg 69120, Germany; Medical Faculty and Faculty of Biosciences, Heidelberg University, Im Neuenheimer Feld 234, Heidelberg 69120, Germany; National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg 69120, Germany.
Stephen J PandolDepartment of Medicine, Cedars-Sinai Medical Center and University of California at Los Angeles, Thalians W204 8700 Beverly Blvd. Los Angeles, California CA 90048, United States.
Peter BaileyDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Berliner Str. 41, Heidelberg 69120, Germany; Botton-Champalimaud Pancreatic Cancer Centre, Lisbon, Portugal. Electronic address: peter.bailey@research.fchampalimaud.org.
John P NeoptolemosHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 420, Heidelberg 69120, Germany; Botton-Champalimaud Pancreatic Cancer Centre, Lisbon, Portugal. Electronic address: john.neoptolemos@med.uni-heidelberg.de.

Funding

The paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic nicheP01CA233452 · NCI · CEDARS-SINAI MEDICAL CENTER · PI BHOWMICK, NEIL A., LU, SHELLY CHI-LOO · 2020 to 2024
$9.5M
NCI NIH HHS P01 CA233452
6 · The paper itself

Abstract

backgroundDespite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-β and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics.

methodsThirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data.

resultsMetavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TS

conclusionsMetavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.

Indexed as

ApoptosisAutophagyGSK3-βHistone deacetylasesMolecular subtypesPancreatic cancer

Identifiers

PMID39217851
PMCPMC11402625

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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.