Evidence map›Paper›PMID 23963286›Full record

ArticleMelanoma research2013

The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity.

David M Woods, Karrune Woan, Fengdong Cheng, Hongwei Wang, Patricio Perez-Villarroel, Calvin Lee, Maritza Lienlaf, Peter Atadja, Edward Seto, Jeffrey Weber and 2 more

Open access · greenAbstract read
In one paragraph

Article in Melanoma research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

63 citing papers in PubMed, 101 citations in OpenAlex.

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  18. Remodeling "cold" tumor immune microenvironmentActa pharmaceutica Sinica. B · 2022
    Article
  19. Drugging the Epigenome: Overcoming Resistance to Targeted and Immunotherapies in Melanoma.JID innovations : skin science from molecules to population health · 2022
    Review
  20. Article

3 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

12 authors at 5 institutions in 2 countries.

David M WoodsDepartment of Immunology, H Lee Moffitt Cancer and Research Institute, Tampa, Florida 33612, USA.
Karrune Woan
Fengdong Cheng
Hongwei Wang
Patricio Perez-Villarroel
Calvin Lee
Maritza Lienlaf
Peter Atadja
Edward Seto
Jeffrey Weber
Eduardo M Sotomayor
Alejandro Villagra
Moffitt Cancer Center · USUniversity of South Florida · USMolecular Oncology (United States) · USNovartis (France) · FRPalmetto Hematology Oncology · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Tissue, Pathology and BioinformaticsP50CA168536 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI MULE, JAMES J. · 2013 to 2017
$8.5M
Regulation of Cross-Tolerance to Tumor AntigensR01CA100850 · NCI · H. LEE MOFFITT CANCER CTR &RES INST · PI SOTOMAYOR, EDUARDO M. · 2003 to 2015
$2.8M
Role of Histone Deacetylases 6 and 11 in regulation of IL-10 and immune responsesR21CA153246 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI VILLAGRA, ALEJANDRO V · 2011 to 2012
$400k
NCI NIH HHS CA100850NCI NIH HHS CA153246NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA168536NCI NIH HHS R01 CA100850NCI NIH HHS R21 CA153246
6 · The paper itself

Abstract

Melanoma is the deadliest skin cancer, and its incidence has been increasing faster than any other cancer. Although immunogenic, melanoma is not effectively cleared by host immunity. In this study, we investigate the therapeutic, antimelanoma potential of the histone deacetylase inhibitor (HDACi) panobinostat (LBH589) by assessing both its cytotoxic effects on melanoma cells as well as enhancement of immune recognition of melanoma. Utilizing murine and human melanoma cell lines, we analyzed the effects of LBH589 on proliferation and survival. In addition, we analyzed the expression of several immunologically relevant surface markers and melanoma differentiation antigens, and the ability of LBH589-treated melanoma to activate antigen-specific T cells. Finally, we assessed the in-vivo effects of LBH589 in a mouse melanoma model. Low nanomolar concentrations of LBH589 inhibit the growth of all melanoma cell lines tested, but not normal melanocytes. This inhibition is characterized by increased apoptosis as well as a G1 cell cycle arrest. In addition, LBH589 augments the expression of major histocompatibility complex and costimulatory molecules on melanoma cells leading to an increased ability to activate antigen-specific T cells. Treatment also increases expression of melanoma differentiation antigens. In vivo, LBH589 treatment of melanoma-bearing mice results in a significant increase in survival. However, in immunodeficient mice, the therapeutic effect of LBH589 is lost. Taken together, LBH589 exerts a dual effect upon melanoma cells by affecting not only growth/survival but also by increasing melanoma immunogenicity. These effects provide the framework for future evaluation of this HDAC inhibitor in melanoma treatment.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalDose-Response Relationship, DrugG1 Phase Cell Cycle CheckpointsHistone Deacetylase InhibitorsHumansHydroxamic AcidsImmunity, CellularImmunocompromised HostIndolesLymphocyte ActivationLymphocytes, Tumor-InfiltratingAntineoplastic AgentsHistone Deacetylase InhibitorsHydroxamic AcidsIndolesPanobinostat

Identifiers

PMID23963286
PMCPMC4012016
OpenAlexW1999782534

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.