Evidence map›Paper›PMID 26272609›Full record

ArticleThe Journal of biological chemistry2015

Inhibition of oncogenic epidermal growth factor receptor kinase triggers release of exosome-like extracellular vesicles and impacts their phosphoprotein and DNA content.

Laura Montermini, Brian Meehan, Delphine Garnier, Wan Jin Lee, Tae Hoon Lee, Abhijit Guha, Khalid Al-Nedawi, Janusz Rak

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

85 citing papers in PubMed, 123 citations in OpenAlex.

  1. A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2017
    Trial
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25 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 1 country.

Laura MonterminiFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1.
Brian MeehanFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1.
Delphine GarnierFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1.
Wan Jin LeeFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1.
Tae Hoon LeeFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1.
Abhijit Guhathe University of Toronto Health Network, Toronto, Ontario M5G 1L7, and.
Khalid Al-Nedawithe McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Janusz RakFrom the Montreal Children's Hospital, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec H4A 3J1, janusz.rak@mcgill.ca.
McGill University Health Centre · CAMontreal Children's Hospital · CAMcMaster University · CAUniversity Health Network · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Cancer cells emit extracellular vesicles (EVs) containing unique molecular signatures. Here, we report that the oncogenic EGF receptor (EGFR) and its inhibitors reprogram phosphoproteomes and cargo of tumor cell-derived EVs. Thus, phosphorylated EGFR (P-EGFR) and several other receptor tyrosine kinases can be detected in EVs purified from plasma of tumor-bearing mice and from conditioned media of cultured cancer cells. Treatment of EGFR-driven tumor cells with second generation EGFR kinase inhibitors (EKIs), including CI-1033 and PF-00299804 but not with anti-EGFR antibody (Cetuximab) or etoposide, triggers a burst in emission of exosome-like EVs containing EGFR, P-EGFR, and genomic DNA (exo-gDNA). The EV release can be attenuated by treatment with inhibitors of exosome biogenesis (GW4869) and caspase pathways (ZVAD). The content of P-EGFR isoforms (Tyr-845, Tyr-1068, and Tyr-1173), ERK, and AKT varies between cells and their corresponding EVs and as a function of EKI treatment. Immunocapture experiments reveal the presence of EGFR and exo-gDNA within the same EV population following EKI treatment. These findings suggest that targeted agents may induce cancer cells to change the EV emission profiles reflective of drug-related therapeutic stress. We suggest that EV-based assays may serve as companion diagnostics for targeted anticancer agents.

Indexed as

AnimalsAntineoplastic AgentsBiomarkersBrain NeoplasmsCell Line, TumorCetuximabCulture Media, ConditionedDNAErbB ReceptorsEtoposideExosomesExtracellular VesiclesGliomaHumansMiceMice, SCIDAntineoplastic AgentsBiomarkersCanertinibCetuximabCulture Media, ConditioneddacomitinibDNAEGFR protein, humanEGFR protein, mouseErbB ReceptorsEtoposideMorpholinesPhosphoproteinsQuinazolinonesanticancer drugcancercaspaseDNAenzyme inhibitorepidermal growth factor receptor (EGFR)exosome (vesicle)phosphorylationprotein kinase

Identifiers

PMID26272609
PMCPMC4591833
OpenAlexW2261862398

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.