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Updated: Jul 9, 2026
Reprogramming Pancreatic Ductal Adenocarcinoma to Pluripotency
Published on: February 2, 2024
PRMT5 inhibitors: Therapeutic potential in pancreatic cancer
Carolin Schneider1, Valentina Spielmann2, Christian J Braun3
1Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, 37075, Germany; Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, Göttingen, 37075, Germany.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is predominantly driven by mutations in the Kirsten rat sarcoma virus (KRAS) oncogene. Due to the pivotal role of KRAS in PDAC pathogenesis, KRAS inhibitors (KRASi) have recently demonstrated initial signs of clinical efficacy. However, considering currently documented response rates and the resistance development to KRASi, additional targeted therapies are needed. In this context, we provide a summary of recent preclinical and clinical findings on protein arginine methyltransferase 5 (PRMT5) inhibitors (PRMT5i) and their implications for PDAC. PRMT5 has been linked to key oncogenic processes, including epithelial-mesenchymal transition (EMT), MYC and Hippo signaling pathways, glycolysis, and therapy resistance. With further advancements and optimization of PRMT5i-based therapies, these inhibitors hold significant potential as therapeutic agents for PDAC treatment. Therefore, we synthesize the current understanding of PRMT5i and highlight promising directions for future developments in PDAC.
Insights
New protein arginine methyltransferase 5 inhibitors (PRMT5i) show promise for pancreatic cancer treatment. These agents target key cancer processes and may overcome resistance to existing KRAS inhibitors (KRASi).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is driven by KRAS mutations, with KRAS inhibitors (KRASi) showing initial clinical efficacy.
- Therapy resistance and limited response rates necessitate the development of additional targeted treatments for PDAC.
- Protein arginine methyltransferase 5 (PRMT5) is implicated in crucial oncogenic pathways relevant to PDAC.
Purpose of the Study:
- To summarize recent preclinical and clinical findings on PRMT5 inhibitors (PRMT5i) for PDAC treatment.
- To explore the role of PRMT5 in PDAC pathogenesis, including its links to EMT, MYC, Hippo signaling, glycolysis, and therapy resistance.
- To highlight the therapeutic potential of PRMT5i and outline future research directions in PDAC.
Main Methods:
- Review of preclinical studies on PRMT5 inhibitors in PDAC models.
- Analysis of clinical trial data involving PRMT5 inhibitors.
- Synthesis of current literature on PRMT5 function in cancer biology.
Main Results:
- PRMT5 plays a role in epithelial-mesenchymal transition (EMT), MYC and Hippo signaling, and glycolysis.
- PRMT5 inhibition has demonstrated preclinical efficacy in PDAC models.
- PRMT5 is associated with the development of resistance to targeted therapies.
Conclusions:
- PRMT5 inhibitors represent a promising therapeutic strategy for PDAC.
- Targeting PRMT5 may overcome resistance mechanisms associated with KRAS inhibitors.
- Further development and optimization of PRMT5i-based therapies are warranted for PDAC treatment.
