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胰腺癌的新兴生物标志物:从早期检测到个性化治疗

Emerging biomarkers for pancreatic cancer: from early detection to personalized therapy.

作者信息

Jamal Mohd Haris, Porel Pratyush, Aran Khadga Raj

机构信息

Department of Pharmacy Practice, ISF College of Pharmacy, GT Road, Moga, Punjab, 142001, India.

Department of Pharmacology, ISF College of Pharmacy, GT Road, Moga, Punjab, 142001, India.

出版信息

Clin Transl Oncol. 2025 May 10. doi: 10.1007/s12094-025-03947-5.

DOI:10.1007/s12094-025-03947-5
PMID:40348906
Abstract

Pancreatic cancer (PC) remains one of the most lethal malignancies, primarily due to its poor prognosis and late diagnosis. Biomarkers are essential in enhancing diagnostic accuracy, prognostic assessments, and therapeutic strategies, thereby addressing these challenges. Conventional biomarkers, such as CA 19-9, are widely used for monitoring disease progression but have limitations in early detection and specificity, necessitating complementary markers like CEA and MUC1. Emerging genetic biomarkers, including KRAS mutations and TP53 alterations, offer critical insights into tumorigenesis and serve as valuable diagnostic, prognostic, and therapeutic targets. Epigenetic biomarkers, such as DNA methylation and histone modifications, provide additional molecular layers, with aberrant methylation patterns and dysregulated histone modifications influencing tumor aggressiveness and therapy resistance. RNA-based biomarkers, particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play pivotal roles in regulating tumor biology and offer significant diagnostic and therapeutic potential. Protein-based biomarkers, including glycoproteins and cytokines, alongside liquid biopsy components like circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), facilitate real-time disease monitoring and early detection. Personalized therapy is increasingly guided by these biomarkers, which predict responses to chemotherapy and immunotherapy. Despite challenges in biomarker validation and clinical implementation, advancements in multi-omics, artificial intelligence, and collaborative research hold promise for improving patient outcomes and survival rates in PC.

摘要

胰腺癌(PC)仍然是最致命的恶性肿瘤之一,主要原因是其预后较差且诊断较晚。生物标志物对于提高诊断准确性、预后评估和治疗策略至关重要,从而应对这些挑战。传统生物标志物,如CA 19-9,广泛用于监测疾病进展,但在早期检测和特异性方面存在局限性,因此需要CEA和MUC1等互补标志物。新兴的基因生物标志物,包括KRAS突变和TP53改变,为肿瘤发生提供了关键见解,并作为有价值的诊断、预后和治疗靶点。表观遗传生物标志物,如DNA甲基化和组蛋白修饰,提供了额外的分子层面,异常的甲基化模式和失调的组蛋白修饰会影响肿瘤的侵袭性和治疗抗性。基于RNA的生物标志物,特别是微小RNA(miRNA)和长链非编码RNA(lncRNA),在调节肿瘤生物学中起关键作用,并具有显著的诊断和治疗潜力。基于蛋白质的生物标志物,包括糖蛋白和细胞因子,以及循环肿瘤DNA(ctDNA)、外泌体和循环肿瘤细胞(CTC)等液体活检成分,有助于实时疾病监测和早期检测。这些生物标志物越来越多地指导个性化治疗,预测对化疗和免疫治疗的反应。尽管生物标志物验证和临床应用面临挑战,但多组学、人工智能和合作研究的进展有望改善胰腺癌患者的预后和生存率。

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本文引用的文献

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Clinical Advances and Challenges in Targeting KRAS Mutations in Non-Small Cell Lung Cancer.非小细胞肺癌中靶向KRAS突变的临床进展与挑战
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Tumour mutational burden: clinical utility, challenges and emerging improvements.肿瘤突变负担:临床实用性、挑战和新兴的改进。
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High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study.循环肿瘤 DNA 中的高体细胞突变预测转移性胰腺导管腺癌对一线 nab-紫杉醇加 S-1 的反应:前瞻性研究。
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Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer.局部进展期和交界可切除胰腺癌患者的术前化疗、放疗和手术决策。
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Combination immunotherapy for pancreatic cancer: challenges and future considerations.胰腺癌的联合免疫疗法:挑战与未来考量
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Modulation of cellular processes by histone and non-histone protein acetylation.组蛋白和非组蛋白蛋白乙酰化对细胞过程的调节。
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