Evidence map›Paper›PMID 39794830›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands.

Vasudha Mishra, Alka Singh, Michael Korzinkin, Xiangying Cheng, Claudia Wing, Viktoria Sarkisova, Ashwin L Koppayi, Alexandra Pogorelskaya, Oksana Glushchenko, Manu Sundaresan and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Case of MYB-Rearranged Prostatic Adenoid Cystic Carcinoma.Current oncology (Toronto, Ont.) · 2026
    Article
  2. RNA splicing in health and disease.Molecular biomedicine · 2026
    Review
  3. Review
  4. Exploiting Synthetic Lethality of PRMT5 for Precision Treatment of MTAP-Deficient Glioblastoma.International journal of translational medicine (Basel, Switzerland) · 2025
    Article
  5. Review
  6. 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

28 authors.

Vasudha Mishra *Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Alka Singh *Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Michael Korzinkin *Insilico Medicine, Hong Kong, China.
Xiangying ChengDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Claudia WingDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Viktoria SarkisovaInsilico Medicine, Hong Kong, China.
Ashwin L KoppayiDepartment of Medicine, Section of Hematology and Oncology, Northwestern University, Chicago, IL, USA.
Alexandra PogorelskayaInsilico Medicine, Hong Kong, China.
Oksana GlushchenkoInsilico Medicine, Hong Kong, China.
Manu SundaresanDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Venkat ThodimaPrelude Therapeutics, Wilmington, DE, USA.
Jack CarterPrelude Therapeutics, Wilmington, DE, USA.
Koichi ItoPrelude Therapeutics, Wilmington, DE, USA.
Peggy ScherlePrelude Therapeutics, Wilmington, DE, USA.
Anna TrzcinskaDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Ivan OzerovInsilico Medicine, Hong Kong, China.
Everett E VokesDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Grayson ColeDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Frank W PunInsilico Medicine, Hong Kong, China.
Le ShenDepartment of Surgery, University of Chicago, Chicago, IL, USA.
Yuxuan MiaoBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Alexander T PearsonDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Mark W LingenDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Bruce RuggeriPrelude Therapeutics, Wilmington, DE, USA.
Ari J RosenbergDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Alex ZhavoronkovInsilico Medicine, Hong Kong, China. alex@insilicomedicine.com.
Nishant AgrawalDepartment of Surgery, University of Chicago, Chicago, IL, USA. na@uchicago.edu.
Evgeny IzumchenkoDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. izumchen@uchicago.edu.

Funding

Delineating chromatin-related gene expression signatures as a function of HNSCC progressionR01DE027809 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI GAYKALOVA, DARIA A, IZUMCHENKO, EVGENY (EUGENE) G · 2019 to 2023
$2.6M
NIDCR NIH HHS R01 DE027809NIH HHS R01DE027809
6 · The paper itself

Abstract

backgroundAdenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available. As such, identification of new therapeutic targets specific to ACC is crucial for improved patients' outcomes.

methodsAfter thoroughly evaluating the gene expression and signaling patterns characterizing ACC, we applied PandaOmics (an AI-driven software platform for novel therapeutic target discovery) on the unique transcriptomic dataset of 87 primary ACCs. Identifying protein arginine methyl transferase 5 (PRMT5) as a putative candidate with the top-scored druggability, we next determined the applicability of PRMT5 inhibitors (PRT543 and PRT811) using ACC cell lines, organoids, and patient derived xenograft (PDX) models. Molecular changes associated with response to PRMT5 inhibition and anti-proliferative effect of the combination therapy with lenvatinib was then analyzed.

resultsUsing a comprehensive AI-powered engine for target identification, PRMT5 was predicted among potential therapeutic target candidates for ACC. Here we show that monotherapy with selective PRMT5 inhibitors induced a potent anti-tumor activity across several cellular and animal models of ACC, which was paralleled by downregulation of genes associated with ACC tumorigenesis, including MYB and MYC (the recognized drivers of ACC progression). Furthermore, as a subset of genes targeted by lenvatinib is upregulated in ACC, we demonstrate that addition of lenvatinib enhanced the growth inhibitory effect of PRMT5 blockade in vitro, suggesting a potential clinical benefit for patients expressing lenvatinib favorable molecular profile.

conclusionTaken together, our study underscores the role of PRMT5 in ACC oncogenesis and provides a strong rationale for the clinical development of PRMT5 inhibitors as a targeted monotherapy or combination therapy for treatment of patients with this rare disease, based on the analysis of their underlying molecular profile.

Indexed as

Carcinoma, Adenoid CysticProtein-Arginine N-MethyltransferasesSalivary Gland NeoplasmsAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceXenograft Model Antitumor AssaysPRMT5 protein, humanProtein-Arginine N-MethyltransferasesAdenoid cystic carcinoma (ACC)Organoid modelsPandaOmicsPatient derived xenografts (PDXs)Protein arginine methyl transferase 5 (PRMT5)RNA-SeqWhole exome sequencing

Identifiers

PMID39794830
PMCPMC11724466

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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.