Evidence map›Paper›PMID 33032822›Full record

ArticleGynecologic oncology2020

Inhibition of poly(ADP-ribose) polymerase induces synthetic lethality in BRIP1 deficient ovarian epithelial cells.

Marcia A Ciccone, Crystal L Adams, Charles Bowen, Teena Thakur, Charité Ricker, Julie O Culver, Asaf Maoz, Marilena Melas, Gregory E Idos, Anand D Jeyasekharan and 4 more

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

Article in Gynecologic oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 38% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Breast-Ovarian Hereditary Cancer Syndrome: BeyondCurrent oncology (Toronto, Ont.) · 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

14 authors at 6 institutions in 2 countries.

Marcia A CicconeUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: marcia.ciccone@med.usc.edu.
Crystal L AdamsUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Charles BowenDepartment of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, MD Anderson Cancer Center, Houston, TX, USA.
Teena ThakurCancer Science Institute of Singapore, National University of Singapore, Singapore.
Charité RickerUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Julie O CulverUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Asaf MaozDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Marilena MelasThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Gregory E IdosDepartment of Internal Medicine, Division of Gastroenterology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Anand D JeyasekharanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Koji MatsuoUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lynda D RomanUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Stephen B GruberDepartment of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, and Beckman Research Institute, Duarte, CA, USA; Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Kevin J McDonnellDepartment of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, and Beckman Research Institute, Duarte, CA, USA; Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
University of Southern California · USCity Of Hope National Medical Center · USNational University Cancer Institute, Singapore · SGHarvard University · USNationwide Children's Hospital · USThe University of Texas MD Anderson Cancer Center · US

Funding

The Epidemiology of Immune Responses in Colorectal CancerR01CA197350 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GRUBER, STEPHEN B · 2015 to 2019
$3.2M
NCI NIH HHS R01 CA197350
6 · The paper itself

Abstract

objectivePathogenic variations in the homologous recombination (HR) gene, BRCA1 interacting protein C-terminal helicase 1 (BRIP1) increase the risk for ovarian cancer. PARP inhibitors (PARPi) exert a synthetic lethal effect in BRCA-mutated ovarian cancers. Effective HR requires cooperation between BRCA1 and BRIP1; therefore, BRIP1-incompetancy may predict vulnerability to synthetic lethality. Here we investigated the response of ovarian epithelial cells with defective BRIP1 function to PARPi, and compared these cells to those lacking BRCA1 activity.

methodsWe engineered Chinese Hamster ovarian (CHO) epithelial cells to express deficient BRIP1 or BRCA1, and exposed them to olaparib with or without carboplatin or cisplatin. We assessed cellular proliferation and survival; we calculated inhibitory concentrations and combination and reduction drug indices.

resultsBRIP1 and BRCA1 inactivation impedes HR activity, decreases cellular proliferation and compromises DNA damage recovery. Platinum agent exposure impairs cellular survival. Olaparib exposure alone decreases cell viability in BRCA1-deficient cells, although has no effect on BRIP1-deficient cells. Combining carboplatin or cisplatin with olaparib synergistically attenuates cellular survival, consistent with synthetic lethality.

conclusionsBRIP1-deficient ovarian epithelial cells exhibit defective HR, resulting in synthetic lethality when exposed to a platinum agent/PARPi combination. PARPi alone had no effect; this lack of effect may result from distinguishing molecular properties of BRIP1and/or consequences of genomic background. Our study identifies altered BRIP1 as a target for precision medicine-based therapies for ovarian cancers. This investigation supports consideration of the use of a platinum agent/PARPi combination in ovarian cancers depending upon genetic profile and genomic background.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsBRCA1 ProteinCarboplatinCell ProliferationCell SurvivalCHO CellsCisplatinCricetulusDrug SynergismFanconi Anemia Complementation Group ProteinsFemaleHumansMolecular Targeted TherapyOvarian NeoplasmsPhthalazinesBRCA1 ProteinBRCA1 protein, humanBRIP1 protein, humanCarboplatinCisplatinFanconi Anemia Complementation Group ProteinsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsRNA HelicasesBRIP1Genetic predisposition to cancerOvarian cancerPARP inhibitorPlatinum therapeutics

Identifiers

PMID33032822
PMCPMC9893519
OpenAlexW3092468830

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.