Evidence map›Paper›PMID 24292392›Full record

ArticleNature medicine2014

Self-renewal as a therapeutic target in human colorectal cancer.

Antonija Kreso, Peter van Galen, Nicholas M Pedley, Evelyne Lima-Fernandes, Catherine Frelin, Thomas Davis, Liangxian Cao, Ramil Baiazitov, Wu Du, Nadiya Sydorenko and 10 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02404480 (A Phase 1 Study of PTC596 in Patients With Advanced Solid Tumors), which is not on this map. Cited by 280 papers.

0numbers the graph read from it
0cells of the map it votes in
280citing papers in PubMed
24.5field-weighted citation impact, top 1% 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.

NCT02404480 phase1completednot on this mapstarted 2016, after this paper: background citation

A Phase 1 Study of PTC596 in Patients With Advanced Solid Tumors

TypeinterventionalSponsorPTC TherapeuticsRan2016 to 2017Enrolled31ConditionsCancerArmsPTC596
3 · Its place in the literature

Who cites it

280 citing papers in PubMed, 532 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. RNA mCancer communications (London, England) · 2025
    Article
  5. Review
  6. Article
  7. Review
  8. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
    Review
  9. Article
  10. Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

220 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Antonija Kreso1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Peter van GalenPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Nicholas M Pedley1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Evelyne Lima-FernandesStructural Genomics Consortium, Toronto, Ontario, Canada.
Catherine Frelin1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Thomas DavisPTC Therapeutics, South Plainfield, New Jersey, USA.
Liangxian CaoPTC Therapeutics, South Plainfield, New Jersey, USA.
Ramil BaiazitovPTC Therapeutics, South Plainfield, New Jersey, USA.
Wu DuPTC Therapeutics, South Plainfield, New Jersey, USA.
Nadiya SydorenkoPTC Therapeutics, South Plainfield, New Jersey, USA.
Young-Choon MoonPTC Therapeutics, South Plainfield, New Jersey, USA.
Lianne Gibson1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Yadong Wang1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Cherry Leung1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Norman N Iscove1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Cheryl H Arrowsmith1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Structural Genomics Consortium, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Eva SzentgyorgyiDepartment of Pathology, Toronto General Hospital, Toronto, Ontario, Canada.
Steven Gallinger1] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [2] Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
John E Dick1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3].
Catherine A O'Brien1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [3] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [4].
PTC Therapeutics (United States) · USPrincess Margaret Cancer Centre · CAUniversity of Toronto · CAStructural Genomics Consortium · CAToronto General Hospital · CAUniversity Health Network · CA

Funding

CIHRWellcome Trust 092687Wellcome Trust 092809
6 · The paper itself

Abstract

Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1-related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer.

Indexed as

AnimalsBlotting, WesternBromodeoxyuridineCell Line, TumorColorectal NeoplasmsFlow CytometryGenetic VectorsHeterocyclic Compounds, 2-RingHumansLuciferasesMice, Inbred NODMice, SCIDNeoplasm Recurrence, LocalNeoplastic Stem CellsPolycomb Repressive Complex 1RNA InterferenceBMI1 protein, humanBromodeoxyuridineHeterocyclic Compounds, 2-RingLuciferasesPolycomb Repressive Complex 1PTC-209RNA, Small InterferingThiazoles

Identifiers

PMID24292392
OpenAlexW2120997349

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.