Evidence map›Paper›PMID 42745296›Full record

ArticleExperimental hematology & oncology2026

Combination of PARPi and topoisomerase I inhibitors is highly effective in olaparib-resistant ovarian cancer.

M Chiappa, V Villa, F Sias, C Grasselli, L Sala, S Canesi, M Marabese, S Mason, D Dibitetto, R Fruscio and 1 more

Abstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental hematology & oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

M ChiappaLaboratory of Preclinical Gynecological Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
V VillaLaboratory of Preclinical Gynecological Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
F SiasLaboratory of Preclinical Gynecological Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
C GrasselliImmunopharmacology Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
L SalaMouse & Animal Pathology Laboratory (MAPLab), Department of Veterinary Medicine and Animal Sciences, Fondazione UniMi, University of Milano, Lodi, Italy.
S CanesiMouse & Animal Pathology Laboratory (MAPLab), Department of Veterinary Medicine and Animal Sciences, Fondazione UniMi, University of Milano, Lodi, Italy.
M MarabeseLaboratory of Molecular Pharmacology, Department of Experimental Oncology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
S MasonMolecular Oncology & DNA Damage Response Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
D DibitettoMolecular Oncology & DNA Damage Response Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
R FruscioUO Gynecology, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori, University of Milan-Bicocca, Monza, Italy.
G DamiaLaboratory of Preclinical Gynecological Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. giovanna.damia@marionegri.it.

Funding

Fondazione AIRC per la ricerca sul cancro ETS IG30320 and IG33759Ministero dell'Università e della Ricerca PNRR M4C2I1.3 heal Italia project PE00000019 CUP B43D22000710006
6 · The paper itself

Abstract

High-grade serous ovarian carcinoma (HGSOC) often shows an initial response to poly (ADP-ribose) polymerase inhibitors (PARPi) such as olaparib, particularly in tumors with defects in homologous recombination (HR), but resistance to these drugs is a major clinical challenge. To address this, we screened over 1400 FDA-approved compounds to find agents that could restore olaparib sensitivity in resistant ovarian cancer cells. DNA topoisomerase I inhibitors (TOP1i) emerged as the most effective partner. The combination of TOP1 inhibitors with PARPi showed strong synergistic anticancer effects across multiple murine and human HGSOC models, regardless of HR status, including patient-derived xenografts made resistant to olaparib. The combination was well tolerated and primarily worked by inducing apoptosis and increased DNA damage. These findings suggest that TOP1 inhibitors combined with PARP inhibitors could be a promising treatment strategy for olaparib-resistant ovarian cancer.

Indexed as

High throughput screeningOlaparib resistanceOvarian carcinomaPARPiPatient-derived xenograftsSaruparibTopoisomerase I inhibitors

Identifiers

PMID42745296
PMCPMC13579897

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.