Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma - New Molecular Targets for Therapy

Sep 21, 2026

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with low 5-year overall survival, limited effective biomarkers for early detection, and aggressive tumor behavior that drive high mortality. Current immunotherapy and targeted therapy outcomes remain unsatisfactory, motivating new therapeutic strategies. Altered expression of protein arginine methyltransferases (PRMTs) represents a newly described molecular feature, with PRMTs influencing transcription, metabolism, RNA processing, and EMT. Small-molecule PRMT inhibitors are in clinical trials, and the review summarizes PRMT roles in PDAC and their therapeutic potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

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Introduction: Pancreatic Ductal Adenocarcinoma and the Need for New Therapeutics

Review Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy Kritisha Bhandari and Wei-Qun Ding * Citation: Bhandari, K.; Ding, W.-Q. Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy. Int. J. Mol. Sci. 2024, 25, 3958 . [https://doi.org/10.3390/ijms25073958](https://doi.org/10.3390/ijms25073958) Academic Editors: Donatella Delle Cave and Claudio Luchini Received: 29 February 2024 Revised: 28 March 2024 Accepted: 30 March 2024 Published: 2 April 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Department of Pathology, University of Oklahoma Health Sciences Center, BMSB401A, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA; [kritisha-bhandari@ouhsc.edu](kritisha-bhandari@ouhsc.edu) * [Correspondence: weiqun-ding@ouhsc.edu](Correspondence: weiqun-ding@ouhsc.edu); Tel.: +405-271-1605 Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with a low 5-year overall survival rate. It is the third-leading cause of cancer-related deaths in the United States. The lack of robust therapeutics, absence of effective biomarkers for early detection, and aggressive nature of the tumor contribute to the high mortality rate of PDAC. Notably, the outcomes of recent immunotherapy and targeted therapy against PDAC remain unsatisfactory, indicating the need for novel therapeutic strategies. One of the newly described molecular features of PDAC is the altered expression of protein arginine methyltransferases (PRMTs) . PRMTs are a group of enzymes known to methylate arginine residues in both histone and non-histone proteins, thereby mediating cellular homeostasis in biological systems. Some of the PRMT enzymes are known to be overexpressed in PDAC that promotes tumor progression and chemo-resistance via regulating gene transcription, cellular metabolic processes, RNA metabolism, and epithelial mesenchymal transition (EMT) . Small-molecule inhibitors of PRMTs are currently under clinical trials and can potentially become a new generation of anti-cancer drugs. This review aims to provide an overview of the current understanding of PRMTs in PDAC, focusing on their pathological roles and their potential as new therapeutic targets. Keywords: pancreatic ductal adenocarcinoma (PDAC); arginine methylation; protein arginine methyltransferases (PRMTs); molecular targets 1. Introduction: Pancreatic Ductal Adenocarcinoma and the Need for New Therapeutics Pancreatic ductal adenocarcinoma (PDAC) is a major type of pancreatic neoplasm that originates from ductal or acinar cells, comprising more than 90% of pancreatic cancer cases [1] . It is the third-leading cause of cancer-related death in the United States and is predicted to surpass colorectal cancer by 2040, to become the second-leading cause of cancer-related death [2] . The current 5-year overall survival rate for this disease is 13%, which is lower than that for most solid tumor types [3] . Approximately 80–85% of patients are diagnosed with PDAC when the disease has already metastasized or became locally advanced, making them ineligible for surgical resection [4–7] . For the remaining 15–20% of PDAC patients that are diagnosed early and are eligible for surgical resection, 3 out of 4 patients will develop a relapse within 2 years post-operation [7,8] . In both cases, whether considering patients as surgical candidates or patients with metastatic disease, they usually all undergo intensive chemotherapy. The first line of treatment includes the use of two different regimens: FOLFIRINOX, which is the combination of folinic acid (

FAQs

Why is pancreatic ductal adenocarcinoma (PDAC) associated with high mortality?

PDAC has aggressive tumor behavior, low overall survival, and limited effective biomarkers for early detection. Outcomes remain poor even with recent immunotherapy and targeted therapy approaches.

What role do PRMTs play in PDAC biology?

PRMTs are enzymes that methylate arginine residues in histone and non-histone proteins. In PDAC, some PRMT enzymes are overexpressed and contribute to tumor progression and chemo-resistance through effects on gene transcription, cellular metabolism, RNA metabolism, and EMT.

How are current therapies for PDAC administered, and what are their limitations?

Treatment commonly uses intensive chemotherapy such as FOLFIRINOX or gemcitabine with nab-paclitaxel, with second-line regimens for progressing disease. Major challenges include drug resistance (notably with gemcitabine) and significant toxicity, while targeted therapy and immunotherapy show limited effectiveness.

Sep 21, 2026

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