Evidence map›Paper›PMID 30991683›Full record

ReviewCancers2019

Next-Generation Hedgehog/GLI Pathway Inhibitors for Cancer Therapy.

Elisabeth Peer, Suzana Tesanovic, Fritz Aberger

Abstract readReview
In one paragraph

Review in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

49 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
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  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

3 authors.

Elisabeth PeerDepartment of Biosciences, Paris-Lodron University of Salzburg, Cancer Cluster Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria. elisabeth.peer@sbg.ac.at.
Suzana TesanovicDepartment of Biosciences, Paris-Lodron University of Salzburg, Cancer Cluster Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria. suzana.tesanovic@sbg.ac.at.
Fritz AbergerDepartment of Biosciences, Paris-Lodron University of Salzburg, Cancer Cluster Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria. fritz.aberger@sbg.ac.at.ORCID 0000-0003-2009-6305

Funding

Austrian Science Fund P25629
6 · The paper itself

Abstract

The Hedgehog/Glioma-associated oncogene homolog (HH/GLI) signaling pathway regulates self-renewal of rare and highly malignant cancer stem cells (CSC), which have been shown to account for the initiation and maintenance of tumor growth as well as for drug resistance, metastatic spread and relapse. Efficacious therapeutic approaches targeting CSC pathways, such as HH/GLI signaling in combination with chemo, radiation or immunotherapy are, therefore, of high medical need. Pharmacological inhibition of HH/GLI pathway activity represents a promising approach to eliminate malignant CSC. Clinically approved HH/GLI pathway inhibitors target the essential pathway effector Smoothened (SMO) with striking therapeutic efficacy in skin and brain cancer patients. However, multiple genetic and molecular mechanisms resulting in de novo and acquired resistance to SMO inhibitors pose major limitations to anti-HH/GLI therapies and, thus, the eradication of CSC. In this review, we summarize reasons for clinical failure of SMO inhibitors, including mechanisms caused by genetic alterations in HH pathway effectors or triggered by additional oncogenic signals activating GLI transcription factors in a noncanonical manner. We then discuss emerging novel and rationale-based approaches to overcome SMO-inhibitor resistance, focusing on pharmacological perturbations of enzymatic modifiers of GLI activity and on compounds either directly targeting oncogenic GLI factors or interfering with synergistic crosstalk signals known to boost the oncogenicity of HH/GLI signaling.

Indexed as

cancer stem cellsdrug resistanceGLI transcription factorsHedgehog signalingSmoothened inhibitors

Identifiers

PMID30991683
PMCPMC6520835

What OpenQuestion holds

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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.