Evidence map›Paper›PMID 28963969›Full record

ArticleNeoplasia (New York, N.Y.)2017

Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle-Associated PDGFRβ.

Laura J Vella, Andreas Behren, Bradley Coleman, David W Greening, Andrew F Hill, Jonathan Cebon

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

Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

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  18. Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
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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

6 authors at 3 institutions in 1 country.

Laura J VellaOlivia Newton-John Cancer Research Institute, Level 5 Olivia Newton-John Cancer and Wellness Centre, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia; The Florey Institute for Neuroscience and Mental Health, 30 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: ljvella@unimelb.edu.au.
Andreas BehrenOlivia Newton-John Cancer Research Institute, Level 5 Olivia Newton-John Cancer and Wellness Centre, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Heidelberg.
Bradley ColemanDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.
David W GreeningDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.
Andrew F HillDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.
Jonathan CebonOlivia Newton-John Cancer Research Institute, Level 5 Olivia Newton-John Cancer and Wellness Centre, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Heidelberg.
La Trobe University · AUAustin Health · AUFlorey Institute of Neuroscience and Mental Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment of BRAF mutant melanoma with kinase inhibitors has been associated with rapid tumor regression; however, this clinical benefit is short-lived, and most patients relapse. A number of studies suggest that the extracellular environment promotes BRAF inhibitor resistance and tumor progression. Extracellular vesicles, such as exosomes, are functional mediators in the extracellular environment. They are small vesicles known to carry a concentrated group of functional cargo and serve as intercellular communicators not only locally but also systemically. Increasingly, it is reported that extracellular vesicles facilitate the development of drug resistance in cancer; however, their role in BRAF inhibitor resistance in melanoma is unclear. Here we investigated if extracellular vesicles from BRAF inhibitor-resistant melanoma could influence drug sensitivity in recipient melanoma cells. We demonstrate that the resistance driver, PDGFRβ, can be transferred to recipient melanoma cells via extracellular vesicles, resulting in a dose-dependent activation of PI3K/AKT signaling and escape from MAPK pathway BRAF inhibition. These data suggest that the BRAF inhibitor-sensitive phenotype of metastatic melanoma can be altered by delivery of PDGFRβ by extracellular vesicles derived from neighboring drug-resistant melanoma cells.

Indexed as

AnimalsCattleCell ProliferationCoculture TechniquesDose-Response Relationship, DrugDrug Resistance, NeoplasmExosomesExtracellular FluidExtracellular VesiclesHumansIndolesMelanomaProto-Oncogene Proteins B-rafReceptor, Platelet-Derived Growth Factor betaSulfonamidesTumor Cells, CulturedBRAF protein, humanIndolesPDGFRB protein, humanPLX 4720Proto-Oncogene Proteins B-rafReceptor, Platelet-Derived Growth Factor betaSulfonamides

Identifiers

PMID28963969
PMCPMC5678363
OpenAlexW2760567897

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.