Evidence map›Paper›PMID 37550722›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.

Daniele Boso, Martina Tognon, Matteo Curtarello, Sonia Minuzzo, Ilaria Piga, Valentina Brillo, Elisabetta Lazzarini, Jessica Carlet, Ludovica Marra, Chiara Trento and 12 more

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

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. 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

22 authors at 5 institutions in 1 country.

Daniele BosoBasic and Translational Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128, Padova, Italy.
Martina TognonImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Matteo CurtarelloImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Sonia MinuzzoDepartment of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, Padova, 35124, Italy.
Ilaria PigaDepartment of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, Padova, 35124, Italy.
Valentina BrilloDepartment of Biology, University of Padova, Padova, Italy.
Elisabetta LazzariniBasic and Translational Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128, Padova, Italy.
Jessica CarletMedical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Ludovica MarraMedical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Chiara TrentoDepartment of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, Padova, 35124, Italy.
Andrea RasolaDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Ionica MasgrasDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Leonardo CaporaliDepartment of Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, Bologna, Italy.
Fabio Del BenImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO)-IRCCS, Aviano, Italy.
Giulia BrisottoImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO)-IRCCS, Aviano, Italy.
Matteo TurettaImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO)-IRCCS, Aviano, Italy.
Roberta PastorelliLaboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Laura BrunelliLaboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Filippo NavagliaLaboratory Medicine, Department of Medicine-DIMED, University Hospital of Padova, Padova, Italy.
Giovanni EspositoImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Angela GrassiImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Stefano IndraccoloBasic and Translational Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128, Padova, Italy. stefano.indraccolo@unipd.it.ORCID http://orcid.org/0000-0002-4810-7136
Istituto Oncologico Veneto · ITUniversity of Padua · ITCentro di Riferimento Oncologico · ITMario Negri Institute for Pharmacological Research · ITUniversity of Bologna · IT

Funding

Associazione Italiana per la Ricerca sul Cancro IG2020-25179
6 · The paper itself

Abstract

backgroundGenetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis.

methodsClonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy.

resultsTwo clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation.

conclusionA glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy.

Indexed as

GlucoseOvarian NeoplasmsVascular Endothelial Growth Factor AAnimalsCell Line, TumorClone CellsFemaleHumansMiceMice, Inbred NODMice, SCIDOxidative PhosphorylationXenograft Model Antitumor AssaysGlucoseVascular Endothelial Growth Factor AAnti-angiogenic therapyGlucose deprivation resistanceMitochondriaOvarian cancerOxidative phosphorylation

Identifiers

PMID37550722
PMCPMC10405561
OpenAlexW4385616645

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Registered trials

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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.