Evidence map›Paper›PMID 38704133›Full record

ArticleCancer letters2024

BET inhibition decreases HMGCS2 and sensitizes resistant pancreatic tumors to gemcitabine.

Aubrey L Miller, Samuel C Fehling, Rebecca B Vance, Dongquan Chen, Eric Josh Brown, M Iqbal Hossain, Eric O Heard, Shaida A Andrabi, Hengbin Wang, Eddy S Yang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Evaluating TcAs for Use in Biotechnology Applications.Biotech (Basel (Switzerland)) · 2025
    Article
  5. Article
  6. Article
  7. Article
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

14 authors.

Aubrey L MillerDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Samuel C FehlingDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Rebecca B VanceDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Dongquan ChenDepartment of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Eric Josh BrownDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
M Iqbal HossainDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Eric O HeardDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Shaida A AndrabiDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Hengbin WangDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Eddy S YangDepartment of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Donald J BuchsbaumDepartment of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA.
Robert C A M van WaardenburgDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Susan L BellisDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Karina J YoonDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: kyoon@uab.edu.

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
Sialylation-dependent mechanisms driving pancreatic cancer progressionU01CA233581 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BELLIS, SUSAN L, WELLS, LANCE · 2018 to 2022
$2.6M
SULT4a1, a novel neuroprotective protein in strokeR01NS119479 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ANDRABI, SHAIDA A. · 2021 to 2025
$1.9M
Developing novel combination therapies for pancreatic cancerR01CA208272 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YOON, KARINA J · 2017 to 2021
$1.7M
Glycosylation-dependent mechanisms regulating ovarian tumor cell phenotypeR01CA225177 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BELLIS, SUSAN L · 2019 to 2023
$1.6M
Poly(ADP-ribose)-dependent TDP-43 pathology in oxidative stress (R21)R21AG084284 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ANDRABI, SHAIDA A. · 2023 to 2023
$408k
Analysis of SULT4A1 in protein interactionsR21NS116312 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI VAN WAARDENBURG, ROBERT C.A.M. · 2020 to 2020
$408k
NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA208272NCI NIH HHS R01 CA225177NCI NIH HHS U01 CA233581NIA NIH HHS R21 AG084284NINDS NIH HHS R01 NS119479NINDS NIH HHS R21 NS116312
6 · The paper itself

Abstract

Efforts to develop targetable molecular bases for drug resistance for pancreatic ductal adenocarcinoma (PDAC) have been equivocally successful. Using RNA-seq and ingenuity pathway analysis we identified that the superpathway of cholesterol biosynthesis is upregulated in gemcitabine resistant (gemR) tumors using a unique PDAC PDX model with resistance to gemcitabine acquired in vivo. Analysis of additional in vitro and in vivo gemR PDAC models showed that HMG-CoA synthase 2 (HMGCS2), an enzyme involved in cholesterol biosynthesis and rate limiting in ketogenesis, is overexpressed in these models. Mechanistic data demonstrate the novel findings that HMGCS2 contributes to gemR and confers metastatic properties in PDAC models, and that HMGCS2 is BRD4 dependent. Further, BET inhibitor JQ1 decreases levels of HMGCS2, sensitizes PDAC cells to gemcitabine, and a combination of gemcitabine and JQ1 induced regressions of gemR tumors in vivo. Our data suggest that decreasing HMGCS2 may reverse gemR, and that HMGCS2 represents a useful therapeutic target for treating gemcitabine resistant PDAC.

Indexed as

AzepinesCarcinoma, Pancreatic DuctalDeoxycytidineDrug Resistance, NeoplasmGemcitabineHydroxymethylglutaryl-CoA SynthasePancreatic NeoplasmsTriazolesXenograft Model Antitumor AssaysAnimalsAntimetabolites, AntineoplasticBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorFemaleGene Expression Regulation, NeoplasticAntimetabolites, AntineoplasticAzepinesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDeoxycytidineGemcitabineHMGCS2 protein, humanHydroxymethylglutaryl-CoA Synthase(+)-JQ1 compoundTranscription FactorsTriazolesBET bromodomain inhibitor (BETi)Gemcitabine resistance (gemR)HMG-CoA synthase 2 (HMGCS2)Pancreatic cancerPatient-derived xenograft (PDX) models

Identifiers

PMID38704133
PMCPMC11309032

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.