Evidence mapPaperPMID 31936151Full record

ArticleCells2020

Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity.

Mariusz L Hartman, Malgorzata Sztiller-Sikorska, Anna Gajos-Michniewicz, Malgorzata Czyz

Abstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Trametinib-Resistant Melanoma Cells Displaying MITFInternational journal of molecular sciences · 2023
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  17. Article
  18. Review
  19. Article
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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

4 authors.

Mariusz L HartmanDepartment of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.ORCID 0000-0002-2231-3740
Malgorzata Sztiller-SikorskaDepartment of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.ORCID 0000-0001-5827-7959
Anna Gajos-MichniewiczDepartment of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
Malgorzata CzyzDepartment of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.ORCID 0000-0002-8279-4742

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The clinical benefit of MAPK pathway inhibition in BRAF-mutant melanoma patients is limited by the development of acquired resistance. Using drug-naïve cell lines derived from tumor specimens, we established a preclinical model of melanoma resistance to vemurafenib or trametinib to provide insight into resistance mechanisms. Dissecting the mechanisms accompanying the development of resistance, we have shown that (i) most of genetic and non-genetic alterations are triggered in a cell line- and/or drug-specific manner; (ii) several changes previously assigned to the development of resistance are induced as the immediate response to the extent measurable at the bulk levels; (iii) reprogramming observed in cross-resistance experiments and growth factor-dependence restricted by the drug presence indicate that phenotypic plasticity of melanoma cells largely contributes to the sustained resistance. Whole-exome sequencing revealed novel genetic alterations, including a frameshift variant of RBMX found exclusively in phospho-AKT

Indexed as

Adaptation, PhysiologicalBiomarkers, TumorCell Line, TumorCell ProliferationCell SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansMelanomaMitogen-Activated Protein Kinase KinasesMolecular Targeted TherapyNeoplasm ProteinsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesBiomarkers, TumorMitogen-Activated Protein Kinase KinasesNeoplasm ProteinsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesReceptors, Nerve Growth FactorRNA, MessengertrametinibVemurafenibacquired resistanceAXLgrowth factor dependencemelanoma plasticityNGFRpatient-to-patient variabilityRBMXreversible transcriptional reprogrammingtrametinibvemurafenib

Identifiers

PMID31936151
PMCPMC7017165

What Socratic holds

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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 Socratic graph.