Evidence map›Paper›PMID 37087441›Full record

ArticleJournal of ovarian research2023

Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR.

Wenwen Chien, Jeffrey W Tyner, Sigal Gery, Yueyuan Zheng, Li-Yan Li, Mohan Shankar Gopinatha Pillai, Chehyun Nam, Neil A Bhowmick, De-Chen Lin, H Phillip Koeffler

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

Article in Journal of ovarian research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

10 authors at 5 institutions in 3 countries.

Wenwen ChienDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. chienw1@cshs.org.
Jeffrey W TynerKnight Cancer Institute, Oregon Health & Science University, Oregon Health and Science University, 2720 S.W. Moody Avenue, Portland, OR, 97201, USA.
Sigal GeryDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
Yueyuan ZhengClinical Big Data Research Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, P. R. China.
Li-Yan LiThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guandong Province, P. R. China.
Mohan Shankar Gopinatha PillaiDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
Chehyun NamCenter for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Neil A BhowmickDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
De-Chen LinCenter for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90089, USA.
H Phillip KoefflerDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
Cedars-Sinai Medical Center · USUniversity of Southern California · USOregon Health & Science University · USShantou University Medical College · CNThe Seventh Affiliated Hospital of Sun Yat-sen University · CN

Funding

Connecting Genomic Alterations in Liposarcomas with Drug Responses and Identification of New Therapeutic ApproachesR01CA200992 · NCI · CEDARS-SINAI MEDICAL CENTER · PI KOEFFLER, HAROLD PHILLIP · 2016 to 2020
$1.8M
NIH HHS R01-CA200992-04
6 · The paper itself

Abstract

backgroundStandard platinum-based therapy for ovarian cancer is inefficient against ovarian clear cell carcinoma (OCCC). OCCC is a distinct subtype of epithelial ovarian cancer. OCCC constitutes 25% of ovarian cancers in East Asia (Japan, Korea, China, Singapore) and 6-10% in Europe and North America. The cancer is characterized by frequent inactivation of ARID1A and 10% of cases of endometriosis progression to OCCC. The aim of this study was to identify drugs that are either FDA-approved or in clinical trials for the treatment of OCCC.

resultsHigh throughput screening of 166 compounds that are either FDA-approved, in clinical trials or are in pre-clinical studies identified several cytotoxic compounds against OCCC. ARID1A knockdown cells were more sensitive to inhibitors of either mTOR (PP242), dual mTOR/PI3K (GDC0941), ATR (AZD6738) or MDM2 (RG7388) compared to control cells. Also, compounds targeting BH3 domain (AZD4320) and SRC (AZD0530) displayed preferential cytotoxicity against ARID1A mutant cell lines. In addition, WEE1 inhibitor (AZD1775) showed broad cytotoxicity toward OCCC cell lines, irrespective of ARID1A status.

conclusionsIn a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.

Indexed as

Adenocarcinoma, Clear CellAtaxia Telangiectasia Mutated ProteinsOvarian NeoplasmsProtein-Tyrosine KinasesBenzamidesCarcinoma, Ovarian EpithelialCell Cycle ProteinsChinaFemaleHumansIndazolesIndolesMorpholinespara-AminobenzoatesPiperidinesProtein Kinase Inhibitors2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidineAtaxia Telangiectasia Mutated ProteinsATR protein, humanAZD4320BenzamidesCell Cycle ProteinsceralasertibIndazolesIndolesMorpholinespara-AminobenzoatesPiperidinesPP242Protein Kinase InhibitorsProtein-Tyrosine KinasesPurinesPyrimidinesPyrrolidinesRG7388SulfonamidesSulfonesTOR Serine-Threonine KinasesWEE1 protein, humanATROvarian clear cell carcinomaWEE1

Identifiers

PMID37087441
PMCPMC10122390
OpenAlexW4366769577

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.