Evidence map›Paper›PMID 40392598›Full record

ArticleThe Journal of clinical investigation2025

Phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.

Angela Schab, Amanda Compadre, Rebecca Drexler, Megan Loeb, Kevin Rodriguez, Joshua Brill, Shariska Harrington, Carmen Sandoval, Brooke Sanders, Lindsay Kuroki and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Angela SchabDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Amanda CompadreDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Rebecca DrexlerDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Megan LoebDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Kevin RodriguezDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Joshua BrillDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Shariska HarringtonDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.
Carmen SandovalDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Brooke SandersDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Lindsay KurokiDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Carolyn McCourtDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Andrea R HagemannDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Premal ThakerDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
David MutchDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Matthew PowellDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Violeta SerraExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Ian S HagemannDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Ann E WaltsDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Beth Y KarlanDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Sandra OrsulicDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Katherine C FuhDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, California, USA.
Lulu SunDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Priyanka VermaDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Elena LomonosovaDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Peinan ZhaoCenter for Reproductive Health Sciences, Department of Obstetrics and Gynecology, and.
Dineo KhabeleDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
Mary M MullenDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.

Funding

Paul Calabresi Program in Clinical/Translational Research at Mayo ClinicK12CA090628 · NCI · MAYO CLINIC ROCHESTER · PI WEROHA, SARAVUT · 2001 to 2025
$19.7M
Washington University Implementation Science Center for Cancer Control (WU-ISCCC)P50CA244431 · NCI · WASHINGTON UNIVERSITY · PI BROWNSON, ROSS C, COLDITZ, GRAHAM A. · 2019 to 2023
$8.0M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
Epigenetic Drug Regimens for Homologous Recombination Proficient Ovarian Cancer - Diversity SupplementR01CA243511 · NCI · WASHINGTON UNIVERSITY · PI KHABELE, DINEO · 2020 to 2024
$2.5M
Evaluating the impact of Basic needs Assessment and Support to Improve Colposcopy Show rate: The BASICS TrialR03TR004017 · NCATS · WASHINGTON UNIVERSITY · PI KUROKI, LINDSAY M · 2022 to 2023
$157k
BLRD VA I01 BX006020NCATS NIH HHS R03 TR004017NCI NIH HHS K12 CA090628NCI NIH HHS P50 CA244431NCI NIH HHS R01 CA243511NCI NIH HHS T32 CA113275
6 · The paper itself

Abstract

BACKGROUNDTreatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response.METHODSWe evaluated phospho-RPA2-T21 (p-RPA2) foci via immunofluorescence as a biomarker of replication stress in formalin-fixed, paraffin-embedded HGSC samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort, n = 31; validation cohort, n = 244) or PARP inhibitors (n = 63). Recurrent HGSCs (n = 38) were also analyzed. p-RPA2 score was calculated using automated imaging analysis.RESULTSSamples were defined as p-RPA2-high if more than 16% of cells had ≥2 p-RPA2 foci on automated analysis. In the discovery cohort, HR-proficient, p-RPA2-high HGSCs demonstrated significantly higher rates of a chemotherapy response score of 3 to platinum chemotherapy than HR-proficient, p-RPA2-low HGSCs. In the validation cohort, patients with HR-proficient, p-RPA2-high HGSCs had significantly longer survival after platinum treatment than those with HR-proficient, p-RPA2-low HGSCs. Additionally, the p-RPA2 assay effectively predicted survival outcomes in patients treated with PARP inhibitors and in recurrent HGSC samples.CONCLUSIONOur study underscores the importance of considering replication stress markers, such as p-RPA2, alongside HR status in therapeutic planning. This approach has the potential to increase the number of patients receiving effective therapy while reducing unnecessary toxicity.FUNDINGThe Reproductive Scientist Development Program, GOG Foundation, Pilot Translational and Clinical Studies function of the Washington University Institute of Clinical and Translational Sciences, the Foundation for Barnes-Jewish Hospital, Washington University School of Medicine Dean's Scholar Program, The Cancer Biology Pathway Training Grant (5T32CA113275-17), The Lucy, Anarcha, and Betsey (L.A.B.) Award from the Department of Obstetrics and Gynecology at Washington University School of Medicine, and Veterans Affairs Office of Research and Development (I01BX006020).

Indexed as

Biomarkers, TumorHomologous RecombinationNeoplasm ProteinsOvarian NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsAdultAgedFemaleHumansMiddle AgedPlatinumBiomarkers, TumorNeoplasm ProteinsPlatinumPoly(ADP-ribose) Polymerase InhibitorsClinical ResearchDNA repairMolecular diagnosisObstetrics/gynecologyOncology

Identifiers

PMID40392598
PMCPMC12208538

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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.