Evidence map›Paper›PMID 31227503›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019

HDAC Inhibition Enhances the

Fernanda Faião-Flores, Michael F Emmons, Michael A Durante, Fumi Kinose, Biswarup Saha, Bin Fang, John M Koomen, Srikumar P Chellappan, Silvya Stuchi Maria-Engler, Uwe Rix and 3 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 3 pooled it
12.2field-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

72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.

  1. Pooled it
  2. The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024
    Pooled it
  3. Pooled it
  4. Proteogenomic Analysis of HDAC4 and HDAC5 in Uveal Melanoma.Molecular medicine (Cambridge, Mass.) · 2026
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  15. Chimeric Antigen Receptor T Cell with an Inducible Caspase-9 Suicide Gene Eradicates Uveal Melanoma Liver Metastases via B7-H3 Targeting.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
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  18. EHMT2 promotes tumorigenesis inActa pharmaceutica Sinica. B · 2024
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12 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

13 authors at 4 institutions in 2 countries.

Fernanda Faião-FloresThe Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
Michael F EmmonsThe Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
Michael A DuranteBascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0003-3137-6847
Fumi KinoseDepartment of Drug Discovery, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
Biswarup SahaThe Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
Bin FangDepartment of Molecular Oncology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
John M KoomenDepartment of Molecular Oncology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.ORCID 0000-0002-3818-1762
Srikumar P ChellappanThe Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, Florida.ORCID 0000-0003-1216-2966
Silvya Stuchi Maria-EnglerDepartment of Clinical Chemistry and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Uwe RixDepartment of Drug Discovery, The Moffitt Cancer Center & Research Institute, Tampa, Florida.
Jonathan D LichtDivision of Hematology & Oncology, Department of Medicine, University of Florida Health Cancer Center, University of Florida, Gainesville, Florida.ORCID 0000-0002-3942-1369
J William HarbourBascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0002-1104-9809
Keiran S M SmalleyThe Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, Tampa, Florida. keiran.smalley@moffitt.org.
Moffitt Cancer Center · USSylvester Comprehensive Cancer Center · USUniversidade de São Paulo · BRUniversity of Florida Health · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Using Single Cell Analysis to identify therapeutic vulnerabilities in leptomeningeal melanoma metastasesR21CA216756 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI FORSYTH, PETER ALEXANDER, SMALLEY, KEIRAN · 2017 to 2018
$412k
NCI NIH HHS P30 CA076292NCI NIH HHS R21 CA216756
6 · The paper itself

Abstract

purposeThe clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. This study has used multiomics approaches and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance.

resultsWe identified a number of putative escape pathways that were upregulated following MEK inhibition, including the PI3K/AKT pathway, ROR1/2, and IGF-1R signaling. MEK inhibition was also associated with increased GPCR expression, particularly the endothelin B receptor, and this contributed to therapeutic escape through ET-3-mediated YAP signaling. A screen of 289 clinical grade compounds identified HDAC inhibitors as potential candidates that suppressed the adaptive YAP and AKT signaling that followed MEK inhibition.

conclusionsTogether, our studies have identified GPCR-mediated YAP activation and RTK-driven AKT signaling as key pathways involved in the escape of uveal melanoma cells from MEK inhibition. We further demonstrate that HDAC inhibition is a promising combination partner for MEK inhibitors in advanced uveal melanoma.

Indexed as

AnimalsCell Cycle ProteinsCell Line, TumorCell SurvivalDisease Models, AnimalDisease ProgressionDrug Resistance, NeoplasmDrug SynergismHistone Deacetylase InhibitorsHumansMAP Kinase Signaling SystemMelanomaMicePanobinostatPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsCell Cycle ProteinsHistone Deacetylase InhibitorsIGF1R protein, humanPanobinostatPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProteomeProto-Oncogene Proteins c-aktPyridonesPyrimidinonesReceptor, IGF Type 1Receptors, G-Protein-CoupledReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanROR2 protein, humantrametinibTranscription FactorsYY1AP1 protein, human

Identifiers

PMID31227503
PMCPMC6744978
OpenAlexW2949451543

What OpenQuestion holds

Textmetadata
LicenceTDM
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.