Evidence map›Paper›PMID 38202281›Full record

ReviewJournal of clinical medicine2024

WD Repeat Domain 5 Inhibitors for Cancer Therapy: Not What You Think.

April M Weissmiller, Stephen W Fesik, William P Tansey

Abstract readReview
In one paragraph

Review in Journal of clinical medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Expanded profiling of WD repeat domain 5 inhibitors reveals actionable strategies for the treatment of hematologic malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. 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

3 authors.

April M WeissmillerDepartment of Biology, Middle Tennessee State University, Murfreesboro, TN 32132, USA.ORCID 0000-0003-4505-0530
Stephen W FesikDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
William P TanseyDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.ORCID 0000-0002-3900-0978

Funding

Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STEPHEN W. FESIK · 2019 to 2026
$19.6M
Facilitated recruitment of MYC to chromatin by interaction with WDR5R01CA200709 · NCI · VANDERBILT UNIVERSITY · PI TANSEY, WILLIAM PATRICK · 2016 to 2025
$3.9M
Determining the significance of the N-MYC-WDR5 interaction in neuroblastoma.R15CA263868 · NCI · MIDDLE TENNESSEE STATE UNIVERSITY · PI WEISSMILLER, APRIL M. · 2021 to 2021
$380k
CCR NIH HHS HHSN261200800001CNCI NIH HHS CA200709NCI NIH HHS CA236733NCI NIH HHS CA263868NCI NIH HHS HHSN261200800001ENCI NIH HHS P50 CA236733NCI NIH HHS R01 CA200709NCI NIH HHS R15 CA263868
6 · The paper itself

Abstract

WDR5 is a conserved nuclear protein that scaffolds the assembly of epigenetic regulatory complexes and moonlights in functions ranging from recruiting MYC oncoproteins to chromatin to facilitating the integrity of mitosis. It is also a high-value target for anti-cancer therapies, with small molecule WDR5 inhibitors and degraders undergoing extensive preclinical assessment. WDR5 inhibitors were originally conceived as epigenetic modulators, proposed to inhibit cancer cells by reversing oncogenic patterns of histone H3 lysine 4 methylation-a notion that persists to this day. This premise, however, does not withstand contemporary inspection and establishes expectations for the mechanisms and utility of WDR5 inhibitors that can likely never be met. Here, we highlight salient misconceptions regarding WDR5 inhibitors as epigenetic modulators and provide a unified model for their action as a ribosome-directed anti-cancer therapy that helps focus understanding of when and how the tumor-inhibiting properties of these agents can best be understood and exploited.

Indexed as

cancercancer therapyepigeneticMYCPROTACribosomeWDR5

Identifiers

PMID38202281
PMCPMC10779565

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.