Evidence map›Paper›PMID 35908023›Full record

ArticlePharmacological reports : PR2022

The ixabepilone and vandetanib combination shows synergistic activity in docetaxel-resistant MDA-MB-231 breast cancer cells.

Stanton Tam, Yassir Al-Zubaidi, Md Khalilur Rahman, Kirsi Bourget, Fanfan Zhou, Michael Murray

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacological reports : PR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
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  4. Review
  5. 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

6 authors at 1 institution in 1 country.

Stanton Tam *Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, University of Sydney, New South Wales, 2006, Australia.
Yassir Al-Zubaidi *Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, University of Sydney, New South Wales, 2006, Australia.
Md Khalilur RahmanPharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, University of Sydney, New South Wales, 2006, Australia.
Kirsi BourgetPharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, University of Sydney, New South Wales, 2006, Australia.
Fanfan ZhouSydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, New South Wales, 2006, Australia.
Michael MurrayPharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, University of Sydney, New South Wales, 2006, Australia. michael.murray@sydney.edu.au.ORCID http://orcid.org/0000-0002-4233-7619
The University of Sydney · AU

Funding

National Health and Medical Research Council 1145424
6 · The paper itself

Abstract

backgroundThe lack of drug targets is an obstacle to the treatment of patients with triple-negative breast cancer (TNBC). At present, non-specific cytotoxic drugs are first-line agents, but the development of resistance is a major problem with these agents. The epidermal growth factor receptor (EGFR) is a potential target in some TNBCs, because its tyrosine kinase activity drives tumorigenesis. Thus, small molecule inhibitors of the EGFR in combination with cytotoxic agents could be important for the treatment of TNBCs.

methodsThe present study evaluated the efficacies of clinically approved EGFR inhibitors in combination with the cytotoxic agent ixabepilone in parental and docetaxel-resistant MDA-MB-231 cells (231C and TXT cells, respectively). Cell viability was assessed using MTT reduction assays, cell death pathways were evaluated using annexin V/7-aminoactinomycin D staining and flow cytometry and Western immunoblotting was used to assess the expression of pro- and anti-apoptotic proteins in cells.

resultsIxabepilone and the EGFR inhibitors gefitinib and vandetanib inhibited 231C and TXT cell proliferation, but the alternate EGFR inhibitors erlotinib and lapatinib were poorly active. Using combination analysis, ixabepilone/vandetanib was synergistic in both cell types, whereas the ixabepilone/gefitinib combination exhibited antagonism. By flow cytometry, ixabepilone/vandetanib enhanced 231C and TXT cell death over that produced by the single agents and also enhanced caspase-3 cleavage and the pro/anti-apoptotic Bcl-2 protein ratios over ixabepilone alone.

conclusionsThese findings suggest that the ixabepilone/vandetanib combination may have promise for the treatment of patients with drug-resistant TNBC.

Indexed as

Antineoplastic AgentsTriple Negative Breast NeoplasmsAnnexin A5ApoptosisCaspase 3Cell Line, TumorCell ProliferationCytotoxinsDocetaxelEpothilonesErbB ReceptorsErlotinib HydrochlorideGefitinibHumansLapatinibPiperidinesAnnexin A5Antineoplastic AgentsCaspase 3CytotoxinsDocetaxelEpothilonesErbB ReceptorsErlotinib HydrochlorideGefitinibixabepiloneLapatinibPiperidinesProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-2QuinazolinesvandetanibCombination treatmentsDrug resistanceEGFR-receptor inhibitorsIxabepilone

Identifiers

PMID35908023
PMCPMC9584993
OpenAlexW4288855731

What OpenQuestion holds

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LicenceCC BY
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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.