Evidence map›Paper›PMID 31331120›Full record

ArticleCancers2019

Comparative Assessment of Antitumor Effects and Autophagy Induction as a Resistance Mechanism by Cytotoxics and EZH2 Inhibition in INI1-Negative Epithelioid Sarcoma Patient-Derived Xenograft.

Silvia Stacchiotti, Valentina Zuco, Monica Tortoreto, Denis Cominetti, Anna Maria Frezza, Stefano Percio, Valentina Indio, Marta Barisella, Valentina Monti, Silvia Brich and 11 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06680401 (The Evaluation of Cytokines and Hormones as Biomarkers for Epithelioid Haemangioendothelioma and Generation of Patient-derived Preclinical Models to Assess the Activity of Anticancer Agents and Validate Novel Therapeutic Targets), which is not on this map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 18% 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.

NCT06680401 recruitingnot on this mapstarted 2021, after this paper: background citation

The Evaluation of Cytokines and Hormones as Biomarkers for Epithelioid Haemangioendothelioma and Generation of Patient-derived Preclinical Models to Assess the Activity of Anticancer Agents and Validate Novel Therapeutic Targets

TypeobservationalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2021 to 2028Enrolled50ConditionsClinical Presentation, Natural History, Treatment Outcomes
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  3. Review
  4. Translational Aspects of Epithelioid Sarcoma: Current Consensus.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Review
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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

21 authors at 5 institutions in 2 countries.

Silvia StacchiottiAdult Mesenchymal Tumor and Rare Cancer Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it.
Valentina ZucoMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.
Monica TortoretoMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.
Denis CominettiDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via Grassi 74, 20157 Milan, Italy.
Anna Maria FrezzaAdult Mesenchymal Tumor and Rare Cancer Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Stefano PercioMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.ORCID 0000-0002-9362-2639
Valentina IndioInterdepartmental Centre of Cancer Research "Giorgio Prodi", University of Bologna, Via Zambini 33, 40126 Bologna, Italy.ORCID 0000-0002-8854-3821
Marta BarisellaDepartment of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Valentina MontiDepartment of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Silvia BrichDepartment of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Annalisa AstolfiInterdepartmental Centre of Cancer Research "Giorgio Prodi", University of Bologna, Via Zambini 33, 40126 Bologna, Italy.ORCID 0000-0002-2732-0747
Chiara ColomboDepartment of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Sandro PasqualiDepartment of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Marco FoliniMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.ORCID 0000-0002-1811-4407
Mrinal M GounderSarcoma Medical Oncology and Early Drug Development, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Maria A PantaleoInterdepartmental Centre of Cancer Research "Giorgio Prodi", University of Bologna, Via Zambini 33, 40126 Bologna, Italy.
Paola ColliniDepartment of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Angelo Paolo Dei TosDepartment of Medicine, University of Padua School of Medicine, Via Giustiniani 2, 35128 Padua, Italy.
Paolo Giovanni CasaliAdult Mesenchymal Tumor and Rare Cancer Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Alessandro GronchiDepartment of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.ORCID 0000-0002-4703-3534
Nadia ZaffaroniMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.
Fondazione IRCCS Istituto Nazionale dei Tumori · ITUniversity of Bologna · ITMemorial Sloan Kettering Cancer Center · USUniversity of Milan · ITUniversity of Padua · IT

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Ministero della Salute 5 x 1000 funds 2014, grant #13NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Epithelioid sarcoma (ES) is a rare mesenchymal malignancy marked by SMARCB1/INI1 deficiency. Retrospective clinical data report on the activity of anthracycline- and gemcitabine-based regimens. EZH2 inhibitors are currently being tested in clinical trials. Since comparisons of these agents are unlikely to be prospectively evaluated in the clinics, we took advantage of an INI1-deficient proximal-type ES patient-derived xenograft (PDX ES-1) to comparatively assess its preclinical antitumor activity. Mice were treated with doxorubicin and ifosfamide, singly or in combination, gemcitabine, and the EZH2 inhibitor EPZ-011989. Comparable antitumor activity (max tumor volume inhibition: ~90%) was caused by gemcitabine, EPZ-011989, and the doxorubicin-ifosfamide combination. The integration of RNAseq data, generated on tumors obtained from untreated and EPZ-011989-treated mice, and results from functional studies, carried out on the PDX-derived ES-1 cell line, revealed autophagy induction as a possible survival mechanism in residual tumor cells following EPZ-011989 treatment and identified HMGA2 as a main player in this process. Our data support the clinical use of gemcitabine and the doxorubicin-ifosfamide combination, confirm EZH2 as a therapeutic target in proximal-type ES, and suggest autophagy as a cytoprotective mechanism against EZH2 inhibition.

Indexed as

autophagyepithelioid sarcomaEZH2HMGA2PDX

Identifiers

PMID31331120
PMCPMC6678245
OpenAlexW2962847486

What OpenQuestion holds

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Registered trials

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.