PRMT5 inhibitors: Therapeutic potential in pancreatic cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-03-28 DOI:10.1016/j.tranon.2025.102366

Carolin Schneider , Valentina Spielmann , Christian J. Braun , Günter Schneider

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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.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.