Evidence map›Paper›PMID 38454151›Full record

ArticleNPJ precision oncology2024

Connectivity mapping-based identification of pharmacological inhibitor targeting HDAC6 in aggressive pancreatic ductal adenocarcinoma.

Pranita Atri, Ashu Shah, Gopalakrishnan Natarajan, Satyanarayana Rachagani, Sanchita Rauth, Koelina Ganguly, Joseph Carmicheal, Dario Ghersi, Jesse L Cox, Lynette M Smith and 5 more

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

Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
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

15 authors at 3 institutions in 1 country.

Pranita AtriDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-0417-0256
Ashu ShahDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Gopalakrishnan NatarajanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0003-3949-8566
Sanchita RauthDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Koelina GangulyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Joseph CarmichealDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-9669-8241
Dario GhersiSchool of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA.
Jesse L CoxDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-4590-7381
Lynette M SmithDepartment of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
Maneesh JainDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-2020-3687
Sushil KumarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0001-5744-193X
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. p.seshacharyulu@unmc.edu.ORCID http://orcid.org/0000-0002-2348-3901
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. sbatra@unmc.edu.
University of Nebraska Medical Center · USNebraska Medical Center · USUniversity of Nebraska at Omaha · US

Funding

Validation of biomarkers for risk prediction and early diagnosis of Pancreatic AdenocarcinomaU01CA200466 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Surinder K. Batra, Randall Brand · 2016 to 2026
$11.3M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Modulation of Tumor Microenvironment for Improved Therapy of Pancreatic CancerR01CA247471 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., JAIN, MANEESH · 2020 to 2024
$2.8M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Rac1 GTPase in tumorigenesis and progression of pancreatic cancerR01CA206444 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., OUELLETTE, MICHEL M · 2016 to 2020
$1.9M
Targeting Mucin and EGFR Axis in Pancreatic CancerR01CA183459 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2014 to 2018
$1.6M
Seromic Mucin Signature for the Early Diagnosis of Pancreatic CancerR44CA224619 · NCI · SANGUINE DIAGNOSTICS AND THERAPEUTICS · PI JAIN, MANEESH, SOUCHEK, JOSHUA JAMES · 2018 to 2019
$1.5M
Ultrasensitive SERS Nano-Sensors for Pancreatic Cancer Diagnosis and PrognosisR41CA213718 · NCI · SANGUINE DIAGNOSTICS AND THERAPEUTICS · PI JUNKER, WADE M, KAUR, SUKHWINDER · 2016 to 2016
$300k
Combinatorial Biomarkers for Malignant Polyps and Colon Cancer DetectionR43CA235984 · NCI · SANGUINE DIAGNOSTICS AND THERAPEUTICS · PI JAIN, MANEESH, JUNKER, WADE M · 2019 to 2019
$225k
NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA183459NCI NIH HHS R01 CA206444NCI NIH HHS R01 CA210637NCI NIH HHS R01 CA247471NCI NIH HHS R41 CA213718NCI NIH HHS R43 CA235984NCI NIH HHS R44 CA224619NCI NIH HHS U01 CA200466
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to limited therapeutic options and expensive/burdensome drug discovery processes. Utilizing genomic-data-driven Connectivity Mapping (CMAP) to identify a drug closer to real-world PC targeting may improve pancreatic cancer (PC) patient outcomes. Initially, we mapped CMAP data to gene expression from 106 PC patients, identifying nine negatively connected drugs. These drugs were further narrowed down using a similar analysis for PC cell lines, human tumoroids, and patient-derived xenografts datasets, where ISOX emerged as the most potent agent to target PC. We used human and mouse syngeneic PC cells, human and mouse tumoroids, and in vivo mice to assess the ability of ISOX alone and in combination with 5FU to inhibit tumor growth. Global transcriptomic and pathway analysis of the ISOX-LINCS signature identified HDAC 6/cMyc as the target axis for ISOX. Specifically, we discovered that genetic and pharmacological targeting of HDAC 6 affected non-histone protein cMyc acetylation, leading to cMyc instability, thereby disrupting PC growth and metastasis by affecting cancer stemness. Finally, Kras

Identifiers

PMID38454151
PMCPMC10920818
OpenAlexW4392544997

What OpenQuestion holds

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LicenceCC BY
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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.