Evidence map›Paper›PMID 36900361›Full record

ArticleCancers2023

Evaluation of Tazemetostat as a Therapeutically Relevant Substance in Biliary Tract Cancer.

Dino Bekric, Daniel Neureiter, Celina Ablinger, Heidemarie Dobias, Marlena Beyreis, Markus Ritter, Martin Jakab, Johannes Bischof, Ulrich Koller, Tobias Kiesslich and 1 more

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In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
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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

11 authors.

Dino BekricCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.ORCID 0000-0003-3928-519X
Daniel NeureiterInstitute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria.ORCID 0000-0001-9155-5762
Celina AblingerInstitute of Pharmacy, Paracelsus Medical University, 5020 Salzburg, Austria.
Heidemarie DobiasCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.
Marlena BeyreisCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.
Markus RitterCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.ORCID 0000-0001-7346-7750
Martin JakabCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.ORCID 0000-0003-2110-5090
Johannes BischofResearch Program for Molecular Therapy of Genodermatoses, EB House Austria, Department of Dermatology and Allergology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria.ORCID 0000-0001-5309-1936
Ulrich KollerResearch Program for Molecular Therapy of Genodermatoses, EB House Austria, Department of Dermatology and Allergology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria.ORCID 0000-0002-6285-1789
Tobias KiesslichCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.ORCID 0000-0001-5403-9478
Christian MayrCenter of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.

Funding

Austrian Cancer Aid Salzburg ('Österreichische Krebshilfe Salzburg') Austrian Cancer Aid Salzburg ('Österreichische Krebshilfe Salzburg')
6 · The paper itself

Abstract

Biliary tract cancer (BTC) is a gastrointestinal malignancy associated with a poor survival rate. Current therapies encompass palliative and chemotherapeutic treatment as well as radiation therapy, which results in a median survival of only one year due to standard therapeutic ineffectiveness or resistance. Tazemetostat is an FDA-approved inhibitor of enhancer of Zeste homolog 2 (EZH2), a methyltransferase involved in BTC tumorigenesis via trimethylation of histone 3 at lysine 27 (H3K27me3), an epigenetic mark associated with silencing of tumor suppressor genes. Up to now, there are no data available regarding tazemetostat as a possible treatment option against BTC. Therefore, the aim of our study is a first-time investigation of tazemetostat as a potential anti-BTC substance in vitro. In this study, we demonstrate that tazemetostat affects cell viability and the clonogenic growth of BTC cells in a cell line-dependent manner. Furthermore, we found a strong epigenetic effect at low concentrations of tazemetostat, which was independent of the cytotoxic effect. We also observed in one BTC cell line that tazemetostat increases the mRNA levels and protein expression of the tumor suppressor gene Fructose-1,6-bisphosphatase 1 (FBP1). Interestingly, the observed cytotoxic and epigenetic effects were independent of the mutation status of EZH2. To conclude, our study shows that tazemetostat is a potential anti-tumorigenic substance in BTC with a strong epigenetic effect.

Indexed as

biliary tract cancercholangiocarcinomaepigeneticsEZH2 inhibitortazemetostat

Identifiers

PMID36900361
PMCPMC10000745

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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.