Evidence map›Paper›PMID 39403898›Full record

ArticleCancer medicine2024

A High-Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers.

Jenna S Bleloch, Sizhu Lu, Saif Feroz Khan, Karabo Serala, Elena Seraia, Val Millar, Daniel Ebner, Colin Goding, Sharon Prince

Abstract read
In one paragraph

Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

9 authors.

Jenna S BlelochDivision of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Sizhu LuLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Saif Feroz KhanDivision of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Karabo SeralaDivision of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Elena SeraiaTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Val MillarTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Daniel EbnerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Colin GodingLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Sharon PrinceDivision of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.ORCID https://orcid.org/0000-0002-6975-5255

Funding

China Scholars ProgramInternational Centre for Genetic Engineering and Biotechnology, Collaborative Research ProgrammeLudwig Institute for Cancer ResearchNational Research Foundation of South Africa, Competitive Programme for Rated ResearchersNewton RCUK PhD Partnering SchemeSouth African Medical Research Council, Self-Initiated Research GrantUniversity of Cape Town, UCT Vision 2030 Grand Challenges Programme
6 · The paper itself

Abstract

backgroundThe highly homologous T-box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low- and middle-income countries. In the current study, we therefore combined a targeted and drug repurposing approach to identify drugs that are expected to be more efficacious and cost-effective with significantly reduced side effects.

methodsA high-throughput cell-based immunofluorescence screen was performed to identify drugs in the Pharmakon 1600 drug library that can negatively regulate TBX2 and/or TBX3 levels. "Hit" drugs were validated for their effect on TBX2/TBX3 levels and cytotoxicity in TBX2/TBX3-dependent melanoma and rhabdomyosarcoma cells. To this end, immunofluorescence, western blotting, quantitative real-time PCR, and MTT cell viability assays were performed.

resultsNiclosamide, piroctone olamine, and pyrvinium pamoate, were identified as TBX2 and/or TBX3-targeting drugs, and they exhibited cytotoxicity in a TBX2/TBX3-dependent manner. Furthermore, these "Hit" drugs were shown to induce senescence and/or apoptosis.

conclusionsNiclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost-effective therapeutic agents for the treatment of TBX2/TBX3-dependent cancers.

Indexed as

Antineoplastic AgentsDrug RepositioningHigh-Throughput Screening AssaysT-Box Domain ProteinsApoptosisCell Line, TumorCell ProliferationHumansNeoplasmsAntineoplastic AgentsT-Box Domain Protein 2T-Box Domain ProteinsTBX3 protein, humandrug repurposinghigh‐throughput screenT‐box factorstranscription factors

Identifiers

PMID39403898
PMCPMC11474296

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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.