Evidence map›Paper›PMID 33557912›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

Targeting dopamine receptor D2 as a novel therapeutic strategy in endometrial cancer.

Stuart R Pierce, Ziwei Fang, Yajie Yin, Lindsay West, Majdouline Asher, Tianran Hao, Xin Zhang, Katherine Tucker, Allison Staley, Yali Fan and 10 more

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

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 30 citations in OpenAlex.

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  15. Frontiers in pharmacology · 2024
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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

20 authors at 4 institutions in 2 countries.

Stuart R Pierce *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Ziwei Fang *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Yajie YinDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Lindsay WestDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Majdouline AsherDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Tianran HaoDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Xin ZhangDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Katherine TuckerDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Allison StaleyDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Yali FanDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Wenchuan SunDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Dominic T MooreLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Chang XuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yi-Hsuan TsaiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joel ParkerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Varun Vijay PrabhuOncoceutics, Philadelphia, PA, USA.
Joshua E AllenOncoceutics, Philadelphia, PA, USA.
Douglas LeeOmic Insight, LCC, Durham, NC, 27713, USA.
Chunxiao ZhouDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. czhou@med.unc.edu.
Victoria Bae-JumpDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. victoria_baejump@med.unc.edu.
University of North Carolina at Chapel Hill · USBeijing Obstetrics and Gynecology Hospital · CNOncoceutics (United States) · USCapital Medical University · CN

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3M
Obesity-driven Metabolic and Molecular Biomarkers of Metformin Response in Endometrial CancerR37CA226969 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BAE-JUMP, VICTORIA LIN · 2018 to 2024
$2.5M
American Cancer Society RSG CCE 128826National Institutes of Health (US) R37CA226969NCI NIH HHS R37 CA226969NIEHS NIH HHS P30 ES010126
6 · The paper itself

Abstract

backgroundONC201 is a dopamine receptor D2 (DRD2) antagonist that inhibits tumor growth in preclinical models through ClpP activation to induce integrated stress response pathway and mitochondrial events related to inhibition of cell growth, which is being explored in clinical trials for solid tumors and hematological malignancies. In this study, we investigated the anti-tumorigenic effect of ONC201 in endometrial cancer cell lines and a genetically engineered mouse model of endometrial cancer.

methodsCell proliferation was assessed by MTT and colony formation assays. Cell cycle and apoptosis were evaluated by Cellometer. Invasion capacity was tested using adhesion, transwell and wound healing assays. LKB1

resultsIncreasing DRD2 expression in endometrial cancer was significantly associated with grade, serous histology and stage, as well as worse progression free survival and overall survival. Higher expression of DRD2 mRNA was found for the Copy Number High (CNH) subtype when compared to the other subtypes. ONC201 inhibited cell proliferation, induced cell cycle G1 arrest, caused cellular stress and apoptosis and reduced invasion in endometrial cancer cells. Diet-induced obesity promoted endometrial tumor growth while ONC201 exhibited anti-tumorigenic efficacy in the obese and lean LKB1

conclusionONC201 has anti-tumorigenic effects in endometrial cancer cells and a transgenic mouse model of endometrial cancer, and DRD2 expression was documented in both human serous and endometrioid endometrial cancer. These studies support DRD2 antagonism via ONC201 as a promising therapeutic strategy for endometrial cancer that has already demonstrated pharmacodynamic activity and clinical benefit in both serous and endometrioid endometrial cancer patients.

Indexed as

AnimalsCell ProliferationDisease Models, AnimalEndometrial NeoplasmsFemaleHumansMiceMice, TransgenicNeoplasm InvasivenessDRD2Endometrial cancerInvasionONC201Proliferation

Identifiers

PMID33557912
PMCPMC7869513
OpenAlexW3127970204

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.