Evidence map›Paper›PMID 40594589›Full record

ArticleScientific reports2025

Pharmacologic inhibition of BMI1 exerts antitumor effects against MYCN-amplified neuroblastoma, with activation of the p53 pathway.

Masahiro Hirayama, Eri Yamada, Hiromasa Aoki, Kazuya Izumi, Ayumi Amano, Kohki Toriuchi, Koichi Ogami, Mai Nagasaka, Yasumichi Inoue, Hidetoshi Hayashi and 4 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    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

14 authors.

Masahiro HirayamaDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Eri YamadaDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Hiromasa AokiDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Kazuya IzumiDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Ayumi AmanoDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Kohki ToriuchiDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Koichi OgamiDivision of Molecular Oncology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Mai NagasakaDepartment of Cell Signaling, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Yasumichi InoueDepartment of Cell Signaling, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Hidetoshi HayashiDepartment of Cell Signaling, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Satoru TakeshitaDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Hiroki KakitaDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Yasumasa YamadaDepartment of Perinatal and Neonatal Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, 480-1195, Japan.
Mineyoshi AoyamaDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. aomine@phar.nagoya-cu.ac.jp.

Funding

Japan Society for the Promotion of Science 20K08211Japan Society for the Promotion of Science 21K16403Japan Society for the Promotion of Science 23K14984
6 · The paper itself

Abstract

BMI1, a constituent of polycomb repressive complex 1, is overexpressed in a variety of cancers, including neuroblastoma, highlighting its potential as a target for cancer therapeutics. Given the pivotal role of BMI1, a number of inhibitors have been synthesized and assessed for therapeutic efficacy across a spectrum of cancers. In our present study, the BMI1 inhibitors PTC-028 and PTC-209 exhibited selective antitumor activity against MYCN-amplified neuroblastoma. Notably, PTC-028, which exhibited toxicity at lower concentrations, triggered apoptosis in neuroblastoma cells and induced G1-phase accumulation, along with reductions in S-phase and G2/M-phase populations, thereby promoting cell cycle arrest. Thorough RNA sequencing analyses revealed that PTC-028 treatment activated the p53 signaling pathway, suggesting it plays a critical role in the mechanism of apoptosis induction. Moreover, PTC-028 treatment led to decreases in levels of anti-apoptotic proteins, including BCL2 and MCL1. Significantly, PTC-028 also exhibited antitumor efficacy in a mouse xenograft model of human neuroblastoma. These results suggest that BMI1 inhibitors, particularly PTC-028, are promising therapeutic agents for the management of aggressive MYCN-amplified neuroblastomas.

Indexed as

Antineoplastic AgentsNeuroblastomaN-Myc Proto-Oncogene ProteinPolycomb Repressive Complex 1Signal TransductionTumor Suppressor Protein p53AnimalsApoptosisCell Line, TumorCell ProliferationGene AmplificationGene Expression Regulation, NeoplasticHeterocyclic Compounds, 2-RingHumansMiceThiazolesAntineoplastic AgentsBMI1 protein, humanHeterocyclic Compounds, 2-RingMYCN protein, humanN-Myc Proto-Oncogene ProteinPolycomb Repressive Complex 1PTC-209ThiazolesTumor Suppressor Protein p53BMI1MYCNNeuroblastomap53PTC-028

Identifiers

PMID40594589
PMCPMC12218001

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.