Evidence map›Paper›PMID 42044624›Full record

ArticleCancer research communications2026

Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.

Sebastian O Wendel, Grant M Brooke, Changkun Hu, Allison R Sandoval, Pouya Haratipour, Long Gu, Malaney Young, Maryam Zangi, Brittany L Rasche, N S Banerjee and 9 more

Abstract read
In one paragraph

Article in Cancer research communications, 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

19 authors.

Sebastian O WendelCollege of Health and Human Science, Kansas State University, Manhattan, Kansas.ORCID 0000-0002-5515-0968
Grant M BrookeDivision of Biology, Kansas State University, Manhattan, Kansas.ORCID 0009-0004-4027-8143
Changkun HuBasic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, Washington.ORCID 0000-0002-4407-7144
Allison R SandovalDivision of Biology, Kansas State University, Manhattan, Kansas.ORCID 0009-0002-2584-8684
Pouya HaratipourDepartment of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0003-0181-8958
Long GuDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0002-3536-5056
Malaney YoungDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0001-5857-2851
Maryam ZangiDepartment of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0009-0005-7153-3802
Brittany L RascheCollege of Veterinary Medicine, Kansas State University, Manhattan, Kansas.ORCID 0000-0002-6599-4443
N S BanerjeeDepartment of Biochemistry and Molecular Genetics, Heersink School of Medicine, Birmingham, Alabama.ORCID 0000-0002-9180-0323
Jennifer JossartDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0003-3537-9850
Kelly GarvinDepartment of Clinical Sciences, Colorado State University, Fort Collins, Colorado.ORCID 0009-0005-5628-5599
Brian V GeisbrechtDepartment of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas.ORCID 0000-0002-1775-0727
Rachel CiancioloDepartment of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, Ohio.ORCID 0000-0003-1627-2396
Jacob CawleyDepartment of Clinical Sciences, Colorado State University, Fort Collins, Colorado.ORCID 0000-0003-2993-5179
J Jefferson P PerryDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0001-9889-3502
Robert J HickeyDepartment of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0001-5099-8137
Linda H MalkasDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, California.ORCID 0000-0001-7624-8510
Nicholas A WallaceHHS Deans Office, Kansas State University, Manhattan, Kansas.ORCID 0000-0002-3971-716X

Funding

Mentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Douglas E Wright · 2012 to 2026
$63.0M
Sex-specific effects of obestity on Influenza A virus infection and immunityP20GM130448 · NIGMS · KANSAS STATE UNIVERSITY · PI WAITHAKA MWANGI · 2020 to 2026
$15.8M
Structure/Function Studies of Enzyme Inhibitors and their Roles in Innate Immune EvasionR35GM140852 · NIGMS · KANSAS STATE UNIVERSITY · PI Brian V Geisbrecht · 2021 to 2026
$2.3M
Cervical cancer derived xenografts (PDX) and organoid raft cultures to evaluate pathway specific therapeutic agents.R21CA216789 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BANERJEE, NILAM SANJIB · 2019 to 2020
$355k
National Cancer Institute (NCI) P30ACA033572National Cancer Institute (NCI) R15CA242057National Cancer Institute (NCI) T32CA186895National Institute of Allergy and Infectious Diseases (NIAID) R21AI173784NCI NIH HHS R21 CA216789NIGMS NIH HHS P20 GM103418NIGMS NIH HHS P20 GM130448NIGMS NIH HHS R35 GM140852
6 · The paper itself

Abstract

Cervical cancers remain a significant health burden. Limitations on cervical cancer chemotherapeutic intervention caused by toxic side effects are a persistent barrier to care. In this study, we show that the human papillomavirus oncogenes that cause most cervical cancers also increase the levels of a cancer-associated isoform of proliferating cell nuclear antigen (PCNA) known as caPCNA. The abundance of caPCNA is specifically elevated in cervical cancer. Similar to observations in other cancers, we found that a small-molecule inhibitor of caPCNA (AOH1996) selectively killed cell line, organoid, and xenograft models of cervical cancer. Our subsequent molecular analysis identified a novel ability of AOH1996 to induce cell death by disrupting the interaction between PCNA and γ-tubulin, resulting in mitotic arrest. We show AOH1996 selectively induces mitotic death in transformed cells, because these cells attempt to progress through mitosis, rather than decondensing their chromosomes and reforming their nuclear membranes like untransformed control cells. Furthermore, we show that these differences allow AOH1996 to specifically sensitize cervical cancer cells to cisplatin, a frontline chemotherapeutic used to treat cervical cancer. We found that subtherapeutic doses of AOH1996 and cisplatin could reduce cervical cancer xenograft growth and improve survival, similarly to a therapeutic dose of cisplatin without the cisplatin-induced toxicity that restricts care. To our knowledge, this study provides the first evidence that AOH1996 can function as a cisplatin-sensitizing agent in cervical cancer models. SIGNIFICANCE: We identify a novel mechanism by which the small-molecule inhibitor AOH1996 targets cancer-associated PCNA to induce mitotic death in cervical cancer cells. By disrupting PCNA:γ-tubulin interactions, AOH1996 selectively sensitizes tumors to a lower dose of cisplatin, enabling effective therapy with reduced toxicity and suggesting a potential strategy to reduce treatment-associated toxicity.

Indexed as

CisplatinMitosisProliferating Cell Nuclear AntigenUterine Cervical NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorFemaleHumansMiceTubulinXenograft Model Antitumor AssaysAntineoplastic AgentsCisplatinPCNA protein, humanProliferating Cell Nuclear AntigenTubulin

Identifiers

PMID42044624
PMCPMC13213708

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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.