Evidence map›Paper›PMID 42092176›Full record

ArticleBritish journal of cancer2026

JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models.

Min Sil Kang, Nar Bahadur Katuwal, Mithun Ghosh, Sa Deok Hong, Yeong Gyu Jeong, Seong Min Park, Tae Hoen Kim, Seul-Gi Kim, Seung Ryeol Lee, Yong Wha Moon

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Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

10 authors.

Min Sil KangDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Nar Bahadur KatuwalDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Mithun GhoshDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Sa Deok HongDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Yeong Gyu JeongDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Seong Min ParkDepartment of Biomedical Science, The Graduate School, CHA University, Seongnam-si, Republic of Korea.
Tae Hoen KimDepartment of Pathology, CHA Bundang Medical Center, CHA University, Seongnam-si, Republic of Korea.
Seul-Gi KimHematology and Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Republic of Korea.
Seung Ryeol LeeDepartment of Urology, CHA Bundang Medical Center, CHA University, Seongnam-si, Republic of Korea.
Yong Wha MoonHematology and Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Republic of Korea. ymoon@cha.ac.kr.ORCID http://orcid.org/0000-0002-7943-974X

Funding

National Research Foundation of Korea (NRF) NRF-2021R1A6A3A01086364National Research Foundation of Korea (NRF) NRF-2021R1C1C1006882
6 · The paper itself

Abstract

backgroundPoly(ADP-ribose) polymerase (PARP) inhibitors are highly effective therapies for BRCA1/2-mutated tumors. However, most patients eventually develop acquired resistance. Here, we report that JPI-547, a second-generation PARP inhibitor targeting both PARP1/2 and tankyrase, demonstrates potent antitumor activity in olaparib-sensitive and resistant BRCA1/2 mutant models.

methodsOlaparib-resistant (OR) models were generated using BRCA-mutated human ovarian and breast cancer cell lines and ovarian Patient-Derived Tumor Xenograft (PDTX) by exposing to olaparib. For clinical relevance, public mRNA microarray datasets of ovarian and breast cancer were analyzed.

resultsJPI-547 demonstrated better antitumor efficacy in both olaparib-sensitive and resistant BRCA-mutated preclinical models than first-generation PARP inhibitors. Mechanistically, the on-target inhibition of PARP1/2 and tankyrase by JPI-547 strongly inhibited the restoration of homologous recombination (HR) activity by suppressing RAD51 expression. This action resulted in the retardation of tumor growth in olaparib-sensitive and resistant ovarian PDTX models. Furthermore, high RAD51 expression was significantly associated with poor prognosis in ovarian and breast cancer patients based on public mRNA expression data.

conclusionThese results suggest the scientific rationale for further clinical development of JPI-547 for treating both PARP inhibitor-sensitive patients and those resistant to first-generation PARP inhibitors in BRCA-mutated cancers.

Indexed as

BRCA1 ProteinBRCA2 ProteinBreast NeoplasmsOvarian NeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsTankyrasesAnimalsCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMiceMutationPhthalazinesPiperazinesBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanolaparibPARP1 protein, humanPARP2 protein, humanPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTankyrases

Identifiers

PMID42092176
PMCPMC13427753

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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.