{"title":"Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: <i>KRAS</i> and beyond.","authors":"Calogero Ciulla, Claudio Luchini","doi":"10.1080/14737159.2024.2348676","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.</p><p><strong>Areas covered: </strong>Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, <i>KRAS</i> mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in <i>KRAS</i>-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as <i>SMAD4</i> in signet-ring cell carcinoma and <i>TP53</i> in invasive cancers derived from intraductal tubulopapillary neoplasms.</p><p><strong>Expert opinion: </strong>The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the <i>KRAS</i> gene.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Molecular Diagnostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14737159.2024.2348676","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.
Areas covered: Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, KRAS mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in KRAS-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as SMAD4 in signet-ring cell carcinoma and TP53 in invasive cancers derived from intraductal tubulopapillary neoplasms.
Expert opinion: The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the KRAS gene.
期刊介绍：
Expert Review of Molecular Diagnostics (ISSN 1473-7159) publishes expert reviews of the latest advancements in the field of molecular diagnostics including the detection and monitoring of the molecular causes of disease that are being translated into groundbreaking diagnostic and prognostic technologies to be used in the clinical diagnostic setting.
Each issue of Expert Review of Molecular Diagnostics contains leading reviews on current and emerging topics relating to molecular diagnostics, subject to a rigorous peer review process; editorials discussing contentious issues in the field; diagnostic profiles featuring independent, expert evaluations of diagnostic tests; meeting reports of recent molecular diagnostics conferences and key paper evaluations featuring assessments of significant, recently published articles from specialists in molecular diagnostic therapy.
Expert Review of Molecular Diagnostics provides the forum for reporting the critical advances being made in this ever-expanding field, as well as the major challenges ahead in their clinical implementation. The journal delivers this information in concise, at-a-glance article formats: invaluable to a time-constrained community.
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