Evidence map›Paper›PMID 31877948›Full record

ArticleInternational journal of molecular sciences2019

Characterization of Melanoma Cell Lines Resistant to Vemurafenib and Evaluation of Their Responsiveness to EGFR- and MET-Inhibitor Treatment.

Ewelina Dratkiewicz, Aleksandra Simiczyjew, Katarzyna Pietraszek-Gremplewicz, Justyna Mazurkiewicz, Dorota Nowak

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed.

  1. Article
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  5. Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.International journal of molecular sciences · 2024
    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

5 authors.

Ewelina DratkiewiczDepartment of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.ORCID 0000-0002-2389-3513
Aleksandra SimiczyjewDepartment of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.
Katarzyna Pietraszek-GremplewiczDepartment of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.
Justyna MazurkiewiczDepartment of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.ORCID 0000-0002-0105-0021
Dorota NowakDepartment of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.

Funding

National Science Centre 2014/15/B/NZ5/01467
6 · The paper itself

Abstract

Constitutively active mutated BRAF kinase occurs in more than 40% of patients suffering from melanoma. To block its activity, a specific inhibitor, vemurafenib, is applied as a therapy. Unfortunately, patients develop resistance to this drug rather quickly. Previously, we demonstrated that pairs of inhibitors directed against EGFR (epidermal growth factor receptor) and MET (hepatocyte growth factor receptor) trigger a synergistic cytotoxic effect in human melanoma cells, and decrease their invasive abilities. In this study, we aimed to generate and characterize melanoma cells resistant to vemurafenib treatment, and then to evaluate the effectiveness of a previously developed therapy in this model. We showed that melanoma cells resistant to the BRAF inhibitor are characterized by a lower proliferation rate and they acquire a spindle-like shape. Using Western Blot, we also noticed increased levels of EGFR, MET, and selected markers of cancer stem cells in generated cell lines. Resistant cells also exhibited increased invasive abilities and elevated proteolytic activity, observed using scratch wound assays and gelatin zymography. Moreover, combination therapy reduced their viability, as measured with a colorimetric cytotoxicity test, and decreased invasiveness. The obtained results validate the application of combination therapy directed against EGFR and MET in melanoma cells resistant to treatment with inhibitors of mutated BRAF.

Indexed as

Drug Resistance, NeoplasmMelanomaMutationProto-Oncogene Proteins c-metAntineoplastic AgentsCell Line, TumorErbB ReceptorsHumansProto-Oncogene Proteins B-rafVemurafenibAntineoplastic AgentsBRAF protein, humanEGFR protein, humanErbB ReceptorsMET protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-metVemurafenibBRAFcancer stem cellsdrug resistanceEGFRforetinibinvasionlapatinibmelanomaMETvemurafenib

Identifiers

PMID31877948
PMCPMC6981576

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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.