胰腺癌生物侵袭性和不良预后的基因组决定因素:KRAS 及其他

IF 3.9 3区 医学 Q1 PATHOLOGY Expert Review of Molecular Diagnostics Pub Date : 2024-05-01 Epub Date: 2024-05-06 DOI:10.1080/14737159.2024.2348676
Calogero Ciulla, Claudio Luchini
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引用次数: 0

摘要

导言:胰腺癌具有明显的组织分子异质性。因此,在同一类肿瘤中,不同的肿瘤组织学具有不同的基因组特征:本专家综述以PubMed、SCOPUS和Embase(最后检索日期:2024年4月4日)中的数据为基础,介绍并讨论了胰腺癌生物侵袭性和不良预后的基本分子决定因素。首先,KRAS突变仍然是治疗胰腺癌最关键的难点之一。在该地区,超过 90% 的恶性肿瘤都存在 KRAS 突变。值得注意的是,KRAS突变的胰腺癌通常缺乏可用于分子疗法的可操作改变。此外,基于转录组的研究表明,鳞状表型的特点是预后和对标准化疗的反应较差。我们还讨论了与特定胰腺癌亚组预后不良有关的分子生物标志物,如标志环细胞癌中的 SMAD4 和导管内管状乳头状瘤浸润癌中的 TP53:专家意见:确定预后特别不良的胰腺癌亚组是开展具体研究工作的关键一步。除了实施和加强当前的精准肿瘤学策略外,改善胰腺癌患者生存率的决定性一步必须通过靶向 KRAS 基因来实现。
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Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: KRAS and beyond.

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.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
71
审稿时长
1 months
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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