{"title":"Splicing dysregulation: hallmark and therapeutic opportunity in pancreatic cancer.","authors":"Chiara Naro, Veronica Ruta, Claudio Sette","doi":"10.1016/j.molmed.2024.11.007","DOIUrl":null,"url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer characterized by dismal prognosis. Late diagnosis, resistance to chemotherapy, and lack of efficacious targeted therapies render PDAC almost untreatable. Dysregulation of splicing, the process that excises the introns from nascent transcripts, is emerging as a hallmark of PDAC and a possible vulnerability of this devastating cancer. Splicing factors are deregulated in PDAC and contribute to all steps of tumorigenesis, from inflammation-related early events to metastasis and acquisition of chemoresistance. At the same time, splicing dysregulation offers a therapeutic opportunity to target cancer-specific vulnerabilities. We discuss mounting evidence that splicing plays a key role in PDAC and the opportunities that this essential process offers for developing new targeted therapies.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molmed.2024.11.007","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer characterized by dismal prognosis. Late diagnosis, resistance to chemotherapy, and lack of efficacious targeted therapies render PDAC almost untreatable. Dysregulation of splicing, the process that excises the introns from nascent transcripts, is emerging as a hallmark of PDAC and a possible vulnerability of this devastating cancer. Splicing factors are deregulated in PDAC and contribute to all steps of tumorigenesis, from inflammation-related early events to metastasis and acquisition of chemoresistance. At the same time, splicing dysregulation offers a therapeutic opportunity to target cancer-specific vulnerabilities. We discuss mounting evidence that splicing plays a key role in PDAC and the opportunities that this essential process offers for developing new targeted therapies.
期刊介绍：
Trends in Molecular Medicine (TMM) aims to offer concise and contextualized perspectives on the latest research advancing biomedical science toward better diagnosis, treatment, and prevention of human diseases. It focuses on research at the intersection of basic biology and clinical research, covering new concepts in human biology and pathology with clear implications for diagnostics and therapy. TMM reviews bridge the gap between bench and bedside, discussing research from preclinical studies to patient-enrolled trials. The major themes include disease mechanisms, tools and technologies, diagnostics, and therapeutics, with a preference for articles relevant to multiple themes. TMM serves as a platform for discussion, pushing traditional boundaries and fostering collaboration between scientists and clinicians. The journal seeks to publish provocative and authoritative articles that are also accessible to a broad audience, inspiring new directions in molecular medicine to enhance human health.
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