Evidence map›Paper›PMID 40664640›Full record

ArticleCell death & disease2025

Targeted delivery of the PKMYT1 inhibitor RP-6306 mediates PANoptosis in pancreatic cancer via mitotic catastrophe.

Jingyun Chen, Jianghao Ren, Chaolei Zhang, Yang Lv, Jingbin Zhou, Weiliang Jiang, Chaojie Huang, Liping Cao

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. The microRNA Expression Signature of Lung Adenocarcinoma HarboringInternational journal of molecular sciences · 2026
    Article
  2. Article
  3. Review
  4. Review
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

8 authors.

Jingyun Chen *Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0000-0002-8257-0677
Jianghao Ren *Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Chaolei Zhang *Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yang LvDepartment of Emergency Medcine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jingbin ZhouDepartment of Emergency Medcine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Weiliang JiangDepartment of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Chaojie HuangDepartment of Colon and Rectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. 11918325@zju.edu.cn.
Liping CaoDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. caolipingzju@zju.edu.cn.ORCID http://orcid.org/0000-0003-4810-1495

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82373162Zhejiang Province Public Welfare Technology Application Research Project (Public Welfare Technology Application Research Project of Zhejiang Province) LQ24H160023
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor often diagnosed in advanced stages due to its subtle early symptoms, making surgical options nonviable and requiring systemic chemotherapy. Current treatments mainly utilize gemcitabine, which provides limited efficacy. PKMYT1, a serine/threonine protein kinase crucial for cell cycle regulation, is overexpressed in PDAC and correlates with poor prognosis. Treatment with the PKMYT1 inhibitor RP-6306 promotes rapid mitotic entry, resulting in DNA damage and mitotic catastrophe, thereby inducing PANoptosis. RP-6306 effectively inhibits PDAC growth in vitro and in vivo, and shows enhanced anti-tumor activity when combined with gemcitabine, also reducing metastasis. However, gemcitabine has notable systemic toxicity. To target cancer cells more specifically, we utilized vesicles derived from cell membranes (BxPC-3M) to deliver a combination of RP-6306 and gemcitabine (GEM + RP-6306@BxPC-3M). This formulation effectively targets homotypic tumor cells and significantly inhibits tumor growth both in vitro and in vivo. These findings highlight the role of RP-6306 in inducing PANoptosis, characterize PANoptosis as a novel form of cell death associated with mitotic catastrophe, and confirm the synergistic antitumor activity of RP-6306 and gemcitabine in PDAC. Moreover, GEM + RP-6306@BxPC-3M exhibits improved safety and enhanced antitumor efficacy.

Indexed as

Carcinoma, Pancreatic DuctalMitosisPancreatic NeoplasmsProtein Kinase InhibitorsProtein Serine-Threonine KinasesAnimalsCell Line, TumorCell ProliferationDeoxycytidineFemaleGemcitabineHumansMembrane ProteinsMiceMice, NudeProtein-Tyrosine KinasesadavosertibDeoxycytidineGemcitabineMembrane ProteinsPKMYT1 protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesPyrazolesPyrimidinones

Identifiers

PMID40664640
PMCPMC12263950

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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.