Evidence map›Paper›PMID 33148223›Full record

ArticleBMC cancer2020

RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer.

John J Tentler, Julie Lang, Anna Capasso, Deog Joong Kim, Ely Benaim, Young B Lee, Andrew Eisen, Stacey M Bagby, Sarah J Hartman, Betelehem W Yacob and 5 more

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

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 16% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

15 authors at 3 institutions in 1 country.

John J TentlerDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA. john.tentler@cuanschutz.edu.
Julie LangDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, USA.
Anna CapassoDell Medical School, Department of Oncology, University of Texas at Austin, Austin, TX, USA.
Deog Joong KimRexahn Pharmaceuticals Inc., Rockville, MD, USA.
Ely BenaimRexahn Pharmaceuticals Inc., Rockville, MD, USA.
Young B LeeRexahn Pharmaceuticals Inc., Rockville, MD, USA.
Andrew EisenRexahn Pharmaceuticals Inc., Rockville, MD, USA.
Stacey M BagbyDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
Sarah J HartmanDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
Betelehem W YacobDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
Brian GittlemanDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
Todd M PittsDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
Roberta PelandaDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, USA.
S Gail EckhardtDell Medical School, Department of Oncology, University of Texas at Austin, Austin, TX, USA.
Jennifer R DiamondDivision of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO, 80045, USA.
University of Colorado Anschutz Medical Campus · USThe University of Texas at Austin · USUniversity of Colorado Denver · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Studies of human B cell tolerance, from a humanized mouse model to human beingsR01AI124474 · NIAID · UNIVERSITY OF COLORADO DENVER · PI PELANDA, ROBERTA · 2016 to 2020
$2.3M
Role and mechanisms of the PI3K pathway in B cell toleranceR01AI152535 · NIAID · UNIVERSITY OF COLORADO DENVER · PI PELANDA, ROBERTA · 2020 to 2024
$2.1M
The Development of Novel Individualized Therapy for Triple-Negative Breast CancerK23CA172691 · NCI · UNIVERSITY OF COLORADO DENVER · PI DIAMOND, JENNIFER R. · 2013 to 2017
$859k
NCI NIH HHS K23 CA172691NCI NIH HHS P30 CA046934NIAID NIH HHS R01 AI124474NIAID NIH HHS R01 AI152535NIH HHS 1K23CA172691-01A1NIH HHS 5P30CA046934-25
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited systemic treatment options. RX-5902 is a novel anti-cancer agent that inhibits phosphorylated-p68 and thus attenuates nuclear β-catenin signaling. The purpose of this study was to evaluate the ability of β-catenin signaling blockade to enhance the efficacy of anti-CTLA-4 and anti-PD-1 immune checkpoint blockade in immunocompetent, preclinical models of TNBC.

methodsTreatment with RX-5902, anti-PD-1, anti-CTLA-4 or the combination was investigated in BALB/c mice injected with the 4 T1 TNBC cell line. Humanized BALB/c-Rag2

resultsThe addition of RX-5902 to CTLA-4 or PD-1 inhibitors resulted in decreased tumor growth in the 4 T1 and human immune system and MDA-MB-231 xenograft models. Immunologic analyses demonstrated a significant increase in the number of activated T cells in tumor infiltrating lymphocytes (TILs) with RX-5902 treatment compared to vehicle (p < 0.05). In the RX-5902/nivolumab combination group, there was a significant increase in the percentage of CD4+ T cells in TILs and increased systemic granzyme B production (p < 0.01).

conclusionsConclusions: RX-5902 enhanced the efficacy of nivolumab in a humanized, preclinical model of TNBC. Several changes in immunologic profiles were noted in mice treated with RX-5902 and the combination, including an increase in activated TILs and a decrease in human myeloid populations, that are often associated with immunosuppression in a tumor microenvironment. RX-5902 also was shown to potentiate the effects of checkpoint inhibitors of CTLA4 and the PD-1 inhibitor in the 4 T-1 murine TNBC model. These findings indicate that RX-5902 may have important immunomodulatory, as well as anti-tumor activity, in TNBC when combined with a checkpoint inhibitor.

Indexed as

AnimalsApoptosisbeta CateninCell ProliferationDrug Therapy, CombinationFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMice, NudePiperazinesQuinoxalinesTriple Negative Breast Neoplasmsbeta CateninCTNNB1 protein, humanImmune Checkpoint InhibitorsPiperazinesQuinoxalinesRX-5902Humanized mouse modelsImmunotherapyp68PD-1 inhibitorRX-5902Triple-negative breast cancerβ-Catenin

Identifiers

PMID33148223
PMCPMC7641792
OpenAlexW3095047455

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.