Evidence map›Paper›PMID 30266954›Full record

ArticleNature communications2018

Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Olga Kondrashova, Monique Topp, Ksenija Nesic, Elizabeth Lieschke, Gwo-Yaw Ho, Maria I Harrell, Giada V Zapparoli, Alison Hadley, Robert Holian, Emma Boehm and 21 more

Abstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
202citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

202 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  12. Article
  13. Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Article
  15. HRDetect in Tubo-ovarian Carcinoma: Stratification and Therapeutic Implications.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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142 more citing papers are in PubMed but not listed here.

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

31 authors.

Olga KondrashovaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0003-0022-5149
Monique ToppThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Ksenija NesicThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Elizabeth LieschkeThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Gwo-Yaw HoThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Maria I HarrellDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, 98195, USA.
Giada V ZapparoliOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, 3084, Australia.
Alison HadleyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Robert HolianThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Emma BoehmThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Valerie HeongThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Elaine SanijResearch Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC, 3010, Australia.
Richard B PearsonResearch Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC, 3010, Australia.ORCID http://orcid.org/0000-0001-5919-5090
John J KraisFox Chase Cancer Centre, Philadelphia, PA, 19111, USA.
Neil JohnsonFox Chase Cancer Centre, Philadelphia, PA, 19111, USA.
Orla McNallyRoyal Women's Hospital, Parkville, VIC, 3052, Australia.
Sumitra AnandaRoyal Women's Hospital, Parkville, VIC, 3052, Australia.
Kathryn AlsopResearch Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC, 3010, Australia.
Karla J HuttDepartment of Medicine and Health Sciences, Monash University, Clayton, VIC, 3168, Australia.
Scott H KaufmannDepartments of Oncology and Molecular Pharmacology, Mayo Clinic, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-4900-7145
Kevin K LinClovis Oncology, Boulder, CO, 80301, USA.
Thomas C HardingClovis Oncology, Boulder, CO, 80301, USA.
Nadia TraficanteResearch Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC, 3010, Australia.
Australian Ovarian Cancer Study (AOCS)
Anna deFazioCentre for Cancer Research, The Westmead Institute for Medical Research, Sydney Medical School, The University of Sydney and Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, 2145, Australia.
Iain A McNeishDivision of Cancer, Department of Surgery and Cancer, Imperial College London, Kensington, London, SW7 2AZ, United Kingdom.ORCID http://orcid.org/0000-0002-9387-7586
David D BowtellResearch Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC, 3010, Australia.
Elizabeth M SwisherDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, 98195, USA.
Alexander DobrovicOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, 3084, Australia.
Matthew J WakefieldThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0001-6624-4698
Clare L ScottThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. scottc@wehi.edu.au.ORCID http://orcid.org/0000-0002-3689-5956

Funding

Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
Vaccinating against IGFBP-2 to prevent ovarian cancer relapseP50CA083636 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DRESCHER, CHARLES, URBAN, NICOLE DENISE · 1999 to 2015
$35.1M
Compensatory Mechanisms that Promote Homologous Recombination in BRCA1 Mutant CancersR01CA214799 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Neil Johnson · 2017 to 2026
$4.3M
Cancer Research UK 15973Medical Research Council G0501974Medical Research Council G0601891NCI NIH HHS P50 CA083636NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA214799
6 · The paper itself

Abstract

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.

Indexed as

DNA MethylationXenograft Model Antitumor AssaysAnimalsAntineoplastic AgentsBRCA1 ProteinCell Line, TumorCisplatinFemaleGene DosageHumansIndolesKaplan-Meier EstimateMice, Inbred NODMice, KnockoutMice, SCIDOvarian NeoplasmsAntineoplastic AgentsBRCA1 ProteinCisplatinIndolesPoly(ADP-ribose) Polymerase Inhibitorsrucaparib

Identifiers

PMID30266954
PMCPMC6162272

What OpenQuestion holds

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Registered trials

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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.