Evidence map›Paper›PMID 29704517›Full record

ArticleCancer letters2018

DUOXA1-mediated ROS production promotes cisplatin resistance by activating ATR-Chk1 pathway in ovarian cancer.

Yunxiao Meng, Chi-Wei Chen, Mingo M H Yung, Wei Sun, Jing Sun, Zhuqing Li, Jing Li, Zongzhu Li, Wei Zhou, Stephanie S Liu and 11 more

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

Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.2field-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

45 citing papers in PubMed, 78 citations in OpenAlex.

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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

21 authors at 7 institutions in 3 countries.

Yunxiao MengDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Chi-Wei ChenDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Mingo M H YungDepartment of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Wei SunNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, 20892, USA.
Jing SunDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Zhuqing LiDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Jing LiDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Zongzhu LiDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA.
Wei ZhouDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA; Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Stephanie S LiuDepartment of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Annie N Y CheungDepartment of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Hextan Y S NganDepartment of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
John C BraistedNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, 20892, USA.
Yan KaiGW Cancer Center, The George Washington University, Washington, DC, 20052, USA; Department of Physics, The George Washington University Columbian College of Arts & Sciences, Washington, DC, 20052, USA.
Weiqun PengDepartment of Physics, The George Washington University Columbian College of Arts & Sciences, Washington, DC, 20052, USA.
Alexandros TzatsosGW Cancer Center, The George Washington University, Washington, DC, 20052, USA; Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
Yiliang LiTianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.
Zhijun DaiDepartment of Oncology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: wzheng@mail.nih.gov.
David W ChanDepartment of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. Electronic address: dwchan@hku.hk.
Wenge ZhuDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA; GW Cancer Center, The George Washington University, Washington, DC, 20052, USA. Electronic address: wz6812@gwu.edu.
George Washington University · USUniversity of Hong Kong · HKNational Institutes of Health · USGW Medical Faculty Associates · USChinese Academy of Medical Sciences & Peking Union Medical College · CNSecond Affiliated Hospital of Xi'an Jiaotong University · CNSir Run Run Shaw Hospital · CN

Funding

Drug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6M
The Role of And-1 in DNA Damage ResponseR01CA177898 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2014 to 2018
$1.6M
The Regulation of Cisplatin resistance in ovarian cancerR01CA184717 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA177898NCI NIH HHS R01 CA184717
6 · The paper itself

Abstract

The acquisition of resistance is a major obstacle to the clinical use of platinum drugs for ovarian cancer treatment. Increase of DNA damage response is one of major mechanisms contributing to platinum-resistance. However, how DNA damage response is regulated in platinum-resistant ovarian cancer cells remains unclear. Using quantitative high throughput combinational screen (qHTCS) and RNA-sequencing (RNA-seq), we show that dual oxidase maturation factor 1 (DUOXA1) is overexpressed in platinum-resistant ovarian cancer cells, resulting in over production of reactive oxygen species (ROS). Elevated ROS level sustains the activation of ATR-Chk1 pathway, leading to resistance to cisplatin in ovarian cancer cells. Moreover, using qHTCS we identified two Chk1 inhibitors (PF-477736 and AZD7762) that re-sensitize resistant cells to cisplatin. Blocking this novel pathway by inhibiting ROS, DUOXA1, ATR or Chk1 effectively overcomes cisplatin resistance in vitro and in vivo. Significantly, the clinical studies also confirm the activation of ATR and DOUXA1 in ovarian cancer patients, and elevated DOUXA1 or ATR-Chk1 pathway correlates with poor prognosis. Taken together, our findings not only reveal a novel mechanism regulating cisplatin resistance, but also provide multiple combinational strategies to overcome platinum-resistance in ovarian cancer.

Indexed as

AgedAnimalsAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsBenzodiazepinonesCell Line, TumorCheckpoint Kinase 1CisplatinDrug Resistance, NeoplasmFemaleHumansKaplan-Meier EstimateMembrane ProteinsMiceMice, NudeMiddle Aged3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamideAtaxia Telangiectasia Mutated ProteinsATR protein, humanBenzodiazepinonesCheckpoint Kinase 1CHEK1 protein, humanCisplatinMembrane ProteinsPF 00477736PyrazolesReactive Oxygen SpeciesThiophenesUreaATR-Chk1Cisplatin resistanceDUOXA1High throughput screenOvarian cancerROS

Identifiers

PMID29704517
PMCPMC7474466
OpenAlexW2800007094

What OpenQuestion holds

Textmetadata
LicenceTDM
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.