Evidence map›Paper›PMID 37735513›Full record

ArticleCell death & disease2023

A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer.

EunJung Lee, Suyakarn Archasappawat, Keely Ji, Jocelyn Pena, Virneliz Fernandez-Vega, Ritika Gangaraju, Nitin Sai Beesabathuni, Martin Jean Kim, Qi Tian, Priya S Shah and 3 more

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

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

EunJung Lee *Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Suyakarn Archasappawat *Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Keely Ji *Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Jocelyn PenaThe Herbert Wertheim UF Scripps Institute, High-Throughput Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, 33458, USA.ORCID 0000-0002-1729-0521
Virneliz Fernandez-VegaThe Herbert Wertheim UF Scripps Institute, High-Throughput Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, 33458, USA.
Ritika GangarajuDepartment of Chemical Engineering, College of Engineering, University of California, Davis, Davis, CA, 95616, USA.
Nitin Sai BeesabathuniDepartment of Chemical Engineering, College of Engineering, University of California, Davis, Davis, CA, 95616, USA.
Martin Jean KimDepartment of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Qi TianDepartment of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Priya S ShahDepartment of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Louis ScampaviaThe Herbert Wertheim UF Scripps Institute, High-Throughput Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, 33458, USA.
Timothy P SpicerThe Herbert Wertheim UF Scripps Institute, High-Throughput Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, 33458, USA.
Chang-Il HwangDepartment of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA. cihwang@ucdavis.edu.ORCID 0000-0002-5710-7672
University of California, Davis · USScripps Research Institute · US

Funding

MARC at University of California, DavisT34GM136469 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALDRIN V. GOMES, Crystal D Rogers · 2020 to 2026
$2.8M
Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic CancerR37CA249007 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Chang-il Hwang · 2021 to 2026
$2.1M
Integrated Acoustic Transfer System for HTS Library ManagementS10OD025279 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2018 to 2018
$624k
Tandem Multi-modal Plate Readers for a High Throughput Screening platformS10OD030330 · OD · UNIVERSITY OF FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2021 to 2021
$600k
Identification of Key Regulators in Pancreatic Cancer MetastasisK22CA226037 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HWANG, CHANG-IL · 2018 to 2020
$486k
HTS Drug  Discovery DispensersS10OD026857 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2019 to 2019
$452k
NCI NIH HHS K22 CA226037NCI NIH HHS R37 CA249007NIGMS NIH HHS T34 GM136469NIH HHS S10 OD025279NIH HHS S10 OD026857NIH HHS S10 OD030330
6 · The paper itself

Abstract

Pancreatic cancer is one of the deadliest diseases in human malignancies. Among total pancreatic cancer patients, ~10% of patients are categorized as familial pancreatic cancer (FPC) patients, carrying germline mutations of the genes involved in DNA repair pathways (e.g., BRCA2). Personalized medicine approaches tailored toward patients' mutations would improve patients' outcome. To identify novel vulnerabilities of BRCA2-deficient pancreatic cancer, we generated isogenic Brca2-deficient murine pancreatic cancer cell lines and performed high-throughput drug screens. High-throughput drug screening revealed that Brca2-deficient cells are sensitive to Bromodomain and Extraterminal Motif (BET) inhibitors, suggesting that BET inhibition might be a potential therapeutic approach. We found that BRCA2 deficiency increased autophagic flux, which was further enhanced by BET inhibition in Brca2-deficient pancreatic cancer cells, resulting in autophagy-dependent cell death. Our data suggests that BET inhibition can be a novel therapeutic strategy for BRCA2-deficient pancreatic cancer.

Indexed as

Autophagic Cell DeathPancreatic NeoplasmsAnimalsAutophagyBRCA2 ProteinHumansMicePancreasBRCA2 ProteinBRCA2 protein, humanBRCA2 protein, mouse

Identifiers

PMID37735513
PMCPMC10514057
OpenAlexW4386928824

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.