Evidence map›Paper›PMID 40961924›Full record

ArticleCell reports. Medicine2025

PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis.

Parmanand Malvi, Suresh Bugide, Roshan Dutta, Kiran Kumar Reddi, Yvonne J K Edwards, Kamaljeet Singh, Romi Gupta, Narendra Wajapeyee

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. 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
–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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

8 authors.

Parmanand MalviDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Suresh BugideDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Roshan DuttaDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Kiran Kumar ReddiDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Yvonne J K EdwardsDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Kamaljeet SinghDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA.
Romi GuptaDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA; O'Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, Birmingham, AL 35233, USA. Electronic address: romigup@uab.edu.
Narendra WajapeyeeDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA; O'Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, Birmingham, AL 35233, USA. Electronic address: nwajapey@uab.edu.

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
PRECISION METABOLIC THERAPY OF p53 MUTANT TRIPLE NEGATIVE BREAST CANCERSR01CA233481 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUPTA, ROMI · 2021 to 2025
$1.6M
NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA233481
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, associated with poor response to therapies and high mortality. We identify that phosphodiesterase 7A (PDE7A) is overexpressed in the majority of TNBCs, and a higher level of PDE7A associates with poor prognosis. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway, via the transcription factor IRF1, stimulates the expression of PDE7A in TNBC cells. PDE7A inhibition attenuates TNBC growth in both cell culture and mouse models of TNBC. Inhibition of PDE7A suppresses de novo pyrimidine biosynthesis, in part through the downregulation of the enzyme dihydroorotate dehydrogenase (DHODH). DHODH suppression attenuates TNBC tumor growth, mirroring the effects of PDE7A inhibition, and ectopic DHODH expression rescues PDE7A-inhibition-induced tumor suppression. Pharmacological co-targeting of PDE7A and DHODH potently inhibits TNBC tumor growth and metastasis. These findings identify the PDE7A → DHODH →de novo pyrimidine biosynthesis pathway as a key driver of TNBC, offering additional therapeutic opportunities for TNBC patients.

Indexed as

Cyclic Nucleotide Phosphodiesterases, Type 7PyrimidinesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell ProliferationDihydroorotate DehydrogenaseFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudePhosphatidylinositol 3-KinasesSignal TransductionXenograft Model Antitumor AssaysCyclic Nucleotide Phosphodiesterases, Type 7Dihydroorotate DehydrogenasePhosphatidylinositol 3-KinasespyrimidinePyrimidinesDHODHPDE7Aphosphodiesterasespyrimidine biosynthesistriple-negative breast cancer

Identifiers

PMID40961924
PMCPMC12490241

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Registered trials

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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.