Evidence map›Paper›PMID 37968653›Full record

ArticleBreast cancer research : BCR2023

The BET degrader ZBC260 suppresses stemness and tumorigenesis and promotes differentiation in triple-negative breast cancer by disrupting inflammatory signaling.

Deeksha Sharma, Cody G Hager, Li Shang, Lam Tran, Yongyou Zhu, Aihui Ma, Brian Magnuson, Matthew W Lesko, Max S Wicha, Monika L Burness

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

Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. 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

10 authors at 2 institutions in 1 country.

Deeksha SharmaDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Cody G HagerDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Li ShangDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Lam TranDepartment of Biostatistics, University of Michigan, NCRC 26-319S, SPC 2800, 2800 Plymouth Rd, Ann Arbor, MI, USA.
Yongyou ZhuDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Aihui MaDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Brian MagnusonDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Matthew W LeskoDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Max S WichaDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Monika L BurnessDepartment, Unit, and Laboratories, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. mburness@med.umich.edu.
University of Michigan · USSUNY Upstate Medical University · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Targeting breast cancer stem cellsR35CA197585 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2016 to 2022
$6.4M
NCI NIH HHS P30 CA046592NCI NIH HHS R35 CA197585
6 · The paper itself

Abstract

backgroundBreast cancer stem cells (BCSCs) are resistant to standard therapies, facilitate tumor dissemination, and contribute to relapse and progression. Super-enhancers are regulators of stemness, and BET proteins, which are critical for super-enhancer function, are a potential therapeutic target. Here, we investigated the effects of BET proteins on the regulation of breast cancer stemness using the pan-BET degrader ZBC260.

methodsWe evaluated the effect of ZBC260 on CSCs in TNBC cell lines. We assessed the effect of ZBC260 on cellular viability and tumor growth and measured its effects on cancer stemness. We used RNA sequencing and stemness index to determine the global transcriptomic changes in CSCs and bulk cells and further validated our findings by qPCR, western blot, and ELISA.

resultsZBC260 potently inhibited TNBC growth both in vitro and in vivo. ZBC260 reduced stemness as measured by cell surface marker expression, ALDH activity, tumorsphere number, and stemness index while increasing differentiated cells. GSEA analysis indicated preferential downregulation of stemness-associated and inflammatory genes by ZBC260 in ALDH

conclusionsThe BET degrader ZBC260 is an efficient degrader of BET proteins that suppresses tumor progression and decreases CSCs through the downregulation of inflammatory genes and pathways. Our findings support the further development of BET degraders alone and in combination with other therapeutics as CSC targeting agents.

Indexed as

Breast NeoplasmsTriple Negative Breast NeoplasmsCell DifferentiationCell Line, TumorCell Transformation, NeoplasticFemaleHumansNeoplasm Recurrence, LocalNeoplastic Stem CellsProteinsProteinsBET protein degraderBreast cancerCancer stem cellInflammatory cytokinesZBC260

Identifiers

PMID37968653
PMCPMC10648675
OpenAlexW4388704955

What OpenQuestion 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 OpenQuestion graph.