Evidence map›Paper›PMID 30348991›Full record

ArticleOncogene2019

BMI1 is a therapeutic target in recurrent medulloblastoma.

David Bakhshinyan, Chitra Venugopal, Ashley A Adile, Neha Garg, Branavan Manoranjan, Robin Hallett, Xin Wang, Sujeivan Mahendram, Parvez Vora, Thusyanth Vijayakumar and 28 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
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

20 citing papers in PubMed, 43 citations in OpenAlex.

  1. Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  2. Article
  3. Isolation and Culture of Human Neural Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  4. TheInternational journal of molecular sciences · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Know when to fold 'em: Polycomb complexes in oncogenic 3D genome regulation.Frontiers in cell and developmental biology · 2022
    Review
  12. [Survival of children with recurrent medulloblastoma undergoing sequential therapy: an analysis of 101 cases].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. The molecular biology of medulloblastoma metastasis.Brain pathology (Zurich, Switzerland) · 2020
    Review
  20. Article
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

38 authors at 6 institutions in 3 countries.

David BakhshinyanMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Chitra VenugopalMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Ashley A AdileMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Neha GargMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Branavan ManoranjanMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Robin HallettCell Biology Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5S 1A1, Canada.
Xin WangDevelopmental & Stem Cell Biology Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5S 1A1, Canada.ORCID http://orcid.org/0000-0001-6292-3087
Sujeivan MahendramMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Parvez VoraMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Thusyanth VijayakumarMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Minomi SubapandithaMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Mohini SinghMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Michelle Masayo Kameda-SmithMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Maleeha QaziMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Nicole McFarlaneMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Aneet MannMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Olufemi A AjaniSurgery, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Blake YarascavitchSurgery, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Vijay RamaswamyDevelopmental & Stem Cell Biology Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5S 1A1, Canada.ORCID http://orcid.org/0000-0002-6557-895X
Hamza FarooqDevelopmental & Stem Cell Biology Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5S 1A1, Canada.
Sorana MorrissyDivision of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Liangxian CaoPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Nadiya SydorenkoPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Ramil BaiazitovPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Wu DuPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Josephine SheedyPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Marla WeetallPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Young-Choon MoonPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Chang-Sun LeePTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Jacek M KwiecienDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Kathleen H DelaneyDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Brad DobleMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada.ORCID http://orcid.org/0000-0002-0260-2983
Yoon-Jae ChoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Siddhartha MitraDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-1829-7856
David KaplanCell Biology Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5S 1A1, Canada.
Michael D TaylorDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A1, Canada.
Thomas W DavisPTC Therapeutics, 100 Corporate Court, South Plainfield, NJ, 07080-2400, USA.
Sheila K SinghMcMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4L8, Canada. ssingh@mcmaster.ca.
McMaster University · CAPTC Therapeutics (United States) · USUniversity of Toronto · CAStanford University · USHospital for Sick Children · CAMedical University of Lublin · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor, representing 20% of newly diagnosed childhood central nervous system malignancies. Although advances in multimodal therapy yielded a 5-year survivorship of 80%, MB still accounts for the leading cause of childhood cancer mortality. In this work, we describe the epigenetic regulator BMI1 as a novel therapeutic target for the treatment of recurrent human Group 3 MB, a childhood brain tumor for which there is virtually no treatment option beyond palliation. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naive tumors will provide limited clinical benefit since recurrent metastatic MBs are highly genetically divergent from their primary tumor. Using a small molecule inhibitor against BMI1, PTC-028, we were able to demonstrate complete ablation of self-renewal of MB stem cells in vitro. When administered to mice xenografted with patient tumors, we observed significant reduction in tumor burden in both local and metastatic compartments and subsequent increased survival, without neurotoxicity. Strikingly, serial in vivo re-transplantation assays demonstrated a marked reduction in tumor initiation ability of recurrent MB cells upon re-transplantation of PTC-028-treated cells into secondary recipient mouse brains. As Group 3 MB is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious targeted agent would be rapidly transitioned to clinical trials.

Indexed as

AnimalsCell Line, TumorCell ProliferationCell SurvivalCerebellar NeoplasmsChildEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansMedulloblastomaMiceNeoplastic Stem CellsPolycomb Repressive Complex 1Small Molecule LibrariesTreatment OutcomeUp-RegulationBMI1 protein, humanPolycomb Repressive Complex 1Small Molecule Libraries

Identifiers

PMID30348991
OpenAlexW2896987094

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.