PRMT5 inhibitors: Therapeutic potential in pancreatic cancer
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 d...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332500097X |
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| author | Carolin Schneider Valentina Spielmann Christian J. Braun Günter Schneider |
| author_facet | Carolin Schneider Valentina Spielmann Christian J. Braun Günter Schneider |
| author_sort | Carolin Schneider |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5a5ae3a99bcc4bd09697be750ae28452 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-5a5ae3a99bcc4bd09697be750ae284522025-08-20T02:09:40ZengElsevierTranslational Oncology1936-52332025-05-015510236610.1016/j.tranon.2025.102366PRMT5 inhibitors: Therapeutic potential in pancreatic cancerCarolin Schneider0Valentina Spielmann1Christian J. Braun2Günter Schneider3Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, 37075, Germany; Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, Göttingen, 37075, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, 37075, GermanyDepartment of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, 80337, GermanyDepartment 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; CCC-N (Comprehensive Cancer Center Lower Saxony), Göttingen, 37075, Germany; Institute for Translational Cancer Research and Experimental Cancer Therapy, Technical University Munich, Munich, 81675, Germany; Corresponding author at: University Medical Center Göttingen, Department of General, Visceral and Pediatric Surgery, 37075 Göttingen.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.http://www.sciencedirect.com/science/article/pii/S193652332500097XPancreatic cancerKRASPRMT5ResistanceImmunotherapies |
| spellingShingle | Carolin Schneider Valentina Spielmann Christian J. Braun Günter Schneider PRMT5 inhibitors: Therapeutic potential in pancreatic cancer Translational Oncology Pancreatic cancer KRAS PRMT5 Resistance Immunotherapies |
| title | PRMT5 inhibitors: Therapeutic potential in pancreatic cancer |
| title_full | PRMT5 inhibitors: Therapeutic potential in pancreatic cancer |
| title_fullStr | PRMT5 inhibitors: Therapeutic potential in pancreatic cancer |
| title_full_unstemmed | PRMT5 inhibitors: Therapeutic potential in pancreatic cancer |
| title_short | PRMT5 inhibitors: Therapeutic potential in pancreatic cancer |
| title_sort | prmt5 inhibitors therapeutic potential in pancreatic cancer |
| topic | Pancreatic cancer KRAS PRMT5 Resistance Immunotherapies |
| url | http://www.sciencedirect.com/science/article/pii/S193652332500097X |
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