Evidence map›Paper›PMID 38307028›Full record

ArticleCell chemical biology2024

Identification and characterization of a potent and selective HUNK inhibitor for treatment of HER2+ breast cancer.

Tinslee Dilday, Melissa Abt, Nicole Ramos-Solís, Neetu Dayal, Elizabeth Larocque, Adrian L Oblak, Herman O Sintim, Elizabeth S Yeh

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

Article in Cell chemical biology, 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
0.6field-weighted citation impact, top 32% 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, 2 citations in OpenAlex.

  1. Article
  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

8 authors at 4 institutions in 1 country.

Tinslee DildayDepartment of Pharmacology and Toxicology, Indiana University School of Medicine (IUSM), Simon Cancer Center, Indianapolis, IN 46202, USA.
Melissa AbtDepartment of Pharmacology and Toxicology, Indiana University School of Medicine (IUSM), Simon Cancer Center, Indianapolis, IN 46202, USA.
Nicole Ramos-SolísDepartment of Pharmacology and Toxicology, Indiana University School of Medicine (IUSM), Simon Cancer Center, Indianapolis, IN 46202, USA.
Neetu DayalPurdue Institute for Drug Discovery and Purdue Institute for Cancer Research, Purdue University, Lafayette, IN 47907, USA.
Elizabeth LarocquePurdue Institute for Drug Discovery and Purdue Institute for Cancer Research, Purdue University, Lafayette, IN 47907, USA.
Adrian L OblakDepartment of Radiology and Imaging Sciences, IUSM, Indianapolis, IN 46202, USA.
Herman O SintimDepartment of Chemistry, Purdue University, Lafayette, IN 47907, USA; Purdue Institute for Drug Discovery and Purdue Institute for Cancer Research, Purdue University, Lafayette, IN 47907, USA.
Elizabeth S YehDepartment of Pharmacology and Toxicology, Indiana University School of Medicine (IUSM), Simon Cancer Center, Indianapolis, IN 46202, USA. Electronic address: esyeh@iu.edu.
Indiana University Health · USPurdue University Institute for Cancer ResearchIndiana University – Purdue University Indianapolis · USPurdue University West Lafayette · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Overcoming Resistance in HER2-positive Breast CancerR01CA187305 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI YEH, ELIZABETH S · 2015 to 2019
$1.8M
Tumor cell -TAM Paracrine Signaling in Breast CancerR01CA269508 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI Elizabeth Yeh · 2023 to 2026
$1.8M
NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA082709NCI NIH HHS R01 CA187305NCI NIH HHS R01 CA269508
6 · The paper itself

Abstract

Human epidermal growth factor receptor 2 (HER2)-targeted agents have proven to be effective, however, the development of resistance to these agents has become an obstacle in treating HER2+ breast cancer. Evidence implicates HUNK as an anti-cancer target for primary and resistant HER2+ breast cancers. In this study, a selective inhibitor of HUNK is characterized alongside a phosphorylation event in a downstream substrate of HUNK as a marker for HUNK activity in HER2+ breast cancer. Rubicon has been established as a substrate of HUNK that is phosphorylated at serine (S) 92. Findings indicate that HUNK-mediated phosphorylation of Rubicon at S92 promotes both autophagy and tumorigenesis in HER2/neu+ breast cancer. HUNK inhibition prevents Rubicon S92 phosphorylation in HER2/neu+ breast cancer models and inhibits tumorigenesis. This study characterizes a downstream phosphorylation event as a measure of HUNK activity and identifies a selective HUNK inhibitor that has meaningful efficacy toward HER2+ breast cancer.

Indexed as

Antineoplastic AgentsBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesProtein Kinase InhibitorsProtein Serine-Threonine KinasesAnimalsAutophagy-Related ProteinsCell Line, TumorCell ProliferationFemaleHumansMiceMice, NudePhosphorylationStructure-Activity RelationshipAntineoplastic AgentsAutophagy-Related ProteinsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHUNK protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesRUBCN protein, humanauthophagybreast cancerHER2HUNKRubicon

Identifiers

PMID38307028
PMCPMC11102337
OpenAlexW4391450173

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.