Evidence map›Paper›PMID 25502142›Full record

ArticleNature communications2014

Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma.

Judith Müller, Oscar Krijgsman, Jennifer Tsoi, Lidia Robert, Willy Hugo, Chunying Song, Xiangju Kong, Patricia A Possik, Paulien D M Cornelissen-Steijger, Marnix H Geukes Foppen and 9 more

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

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 406 papers.

0numbers the graph read from it
0cells of the map it votes in
406citing papers in PubMed
16.5field-weighted citation impact, top 1% 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

406 citing papers in PubMed, 624 citations in OpenAlex.

  1. Exploratory Analysis of Biomarkers and Treatment Outcomes from the COLUMBUS Study in BRAF V600E/K-Mutant Advanced or Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  2. Review
  3. LncRNAEpigenetics · 2026
    Article
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  6. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
    Review
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346 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 3 countries.

Judith MüllerDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Oscar KrijgsmanDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Jennifer TsoiDivision of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-1750, USA.
Lidia RobertDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA.
Willy HugoDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA.
Chunying SongDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA.
Xiangju KongDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA.
Patricia A PossikDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Paulien D M Cornelissen-SteijgerDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Marnix H Geukes FoppenDivision of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Kristel KemperDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Colin R GodingLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK.
Ultan McDermottWellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Christian BlankDivision of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
John HaanenDivision of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Thomas G Graeber1] Division of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-1750, USA [2] UCLA Metabolomics Center, Crump Institute for Molecular Imaging, California Nanosystems Institute, UCLA, 570 Westwood Plaza, Building 114, Los Angeles, California 90095-7227, USA [3] Jonsson Comprehensive Cancer Center (JCCC), 8-684 Factor Building, Los Angeles, California 90095-1781, USA.
Antoni Ribas1] Division of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-1750, USA [2] Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA [3] Jonsson Comprehensive Cancer Center (JCCC), 8-684 Factor Building, Los Angeles, California 90095-1781, USA.
Roger S Lo1] Division of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-1750, USA [2] Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, Los Angeles, California 90095-7227, USA [3] Jonsson Comprehensive Cancer Center (JCCC), 8-684 Factor Building, Los Angeles, California 90095-1781, USA.
Daniel S PeeperDivision of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
The Netherlands Cancer Institute · NLUniversity of California, Los Angeles · USCalifornia NanoSystems Institute · USLudwig Cancer Research · GBWellcome Sanger Institute · GB

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RIBAS, ANTONI · 2013 to 2017
$8.4M
Preventing MAPK inhibitor resistance in melanoma by targeting genomic instability and immune resistanceR01CA176111 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROGER S LO · 2013 to 2026
$5.4M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS P01 CA168585NCI NIH HHS R01 CA176111
6 · The paper itself

Abstract

Increased expression of the Microphthalmia-associated transcription factor (MITF) contributes to melanoma progression and resistance to BRAF pathway inhibition. Here we show that the lack of MITF is associated with more severe resistance to a range of inhibitors, while its presence is required for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlate with the expression of several activated receptor tyrosine kinases, most frequently AXL. The MITF-low/AXL-high/drug-resistance phenotype is common among mutant BRAF and NRAS melanoma cell lines. The dichotomous behaviour of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and -low clones in a relapsed patient. Furthermore, drug cocktails containing AXL inhibitor enhance melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas.

Indexed as

Gene Expression Regulation, NeoplasticAminopyridinesAnimalsAntineoplastic AgentsAxl Receptor Tyrosine KinaseBenzamidesCell Line, TumorDrug Resistance, NeoplasmExtracellular Signal-Regulated MAP KinasesHumansImatinib MesylateImidazolesIndolesMelanomaMiceMicrophthalmia-Associated Transcription FactorAminopyridinesAntineoplastic AgentsAxl Receptor Tyrosine KinaseBenzamidesBRAF protein, humandabrafenibExtracellular Signal-Regulated MAP KinasesImatinib MesylateImidazolesIndolesMicrophthalmia-Associated Transcription FactorMITF protein, humanN-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideOximesPiperazinesProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafPyridonesPyrimidinesPyrimidinonesReceptor Protein-Tyrosine KinasesSulfonamidestrametinibVemurafenib

Identifiers

PMID25502142
PMCPMC4428333
OpenAlexW2052005627

What OpenQuestion holds

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Read underepoch 390

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.