Evidence map›Paper›PMID 24862760›Full record

ArticleNeoplasia (New York, N.Y.)2014

VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2.

Jaeyoung J Lim, Kun Yang, Barbie Taylor-Harding, W Ruprecht Wiedemeyer, Ronald J Buckanovich

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03462212 (A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced), which is not on this map. Cited by 80 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 2 pooled it
10.0field-weighted citation impact, top 2% 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.

NCT03462212 phase1 / phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced (Stage III B-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer Preceded by a Phase I Dose Escalation Study on Rucaparib-Bevacizumab Combination

TypeinterventionalSponsorFondazione Policlinico Universitario Agostino Gemelli IRCCSRan2021 to 2025Enrolled290ConditionsAdvanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube CancerArmsCarboplatin, Paclitaxel, Bevacizumab, Rucaparib
3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.

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  17. Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.Arteriosclerosis, thrombosis, and vascular biology · 2024
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20 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Jaeyoung J LimDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Kun YangDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Barbie Taylor-HardingDepartment of Obstetrics and Gynecology, University of California, Los Angeles, CA, USA.
W Ruprecht WiedemeyerDepartment of Obstetrics and Gynecology, University of California, Los Angeles, CA, USA.
Ronald J BuckanovichDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Division of Gynecology and Oncology, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA. Electronic address: ronaldbu@med.umich.edu.
University of Michigan–Ann Arbor · USUniversity of California, Los Angeles · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Targeting Ovarian Tumor Associated Myeloid Cells with Nanoparticles TherapeuticsR01CA163345 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BUCKANOVICH, RONALD J · 2012 to 2016
$1.6M
NCI NIH HHS 1-R01-CA163345-01NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA163345
6 · The paper itself

Abstract

In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133(+) ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition-mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.

Indexed as

Genes, BRCA1Genes, BRCA2AC133 AntigenAnimalsAntigens, CDCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGlycoproteinsHumansNeoplastic Stem CellsOvarian NeoplasmsPeptidesProtein Kinase InhibitorsAC133 AntigenAntigens, CDGlycoproteinsPeptidesPROM1 protein, humanProtein Kinase InhibitorsVascular Endothelial Growth Factor CVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-3

Identifiers

PMID24862760
PMCPMC4094836
OpenAlexW2146373785

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.