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从小处着眼以赢取大局?关于细胞外囊泡在胰腺癌生物标志物发现及新治疗方法中潜在应用的批判性综述。

Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer.

作者信息

Vahabi Mahrou, Comandatore Annalisa, Centra Chiara, Blandino Giovanni, Morelli Luca, Giovannetti Elisa

机构信息

Department of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, Netherlands.

Department of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, Netherlands; General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

出版信息

Semin Cancer Biol. 2023 Dec;97:50-67. doi: 10.1016/j.semcancer.2023.11.003. Epub 2023 Nov 11.

DOI:10.1016/j.semcancer.2023.11.003
PMID:37956937
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.

摘要

胰腺导管腺癌(PDAC)是一种极其致命的癌症形式,尽管进行了大量研究,但5年生存率进展有限。治疗PDAC的主要挑战包括早期检测困难,以及由于其侵袭性的分子和微环境特征而对当前治疗方法产生耐药性。这些挑战凸显了识别经临床验证的生物标志物以进行早期检测和临床管理的重要性。细胞外囊泡(EVs),特别是外泌体,已成为通过运输分子货物进行细胞间通讯的关键介质。最近的研究揭示了它们在PDAC的发生、转移和化疗耐药中的作用。因此,在液体活检中利用EVs有望识别用于早期检测、预后和药物疗效监测的生物标志物。然而,许多限制,包括在分离和表征同质EVs群体方面的挑战,以及缺乏标准化方案,可能会影响涉及将EVs作为生物标志物的研究的可靠性,这突出了谨慎方法的必要性。EVs作为一种有前景的药物递送系统和肿瘤新疗法也受到了相当大的关注。将生物分子或化学药物装载到外泌体中并随后递送至靶细胞可以有效地阻碍肿瘤进展。然而,要确保依赖EVs治疗肿瘤的疗法的准确性和有效性,仍有一些障碍必须克服。在这篇综述中,我们研究了最近的进展和剩余的障碍,探讨了在生物标志物发现以及药物递送载体开发中利用EVs的潜力。

相似文献

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Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer.从小处着眼以赢取大局?关于细胞外囊泡在胰腺癌生物标志物发现及新治疗方法中潜在应用的批判性综述。
Semin Cancer Biol. 2023 Dec;97:50-67. doi: 10.1016/j.semcancer.2023.11.003. Epub 2023 Nov 11.
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Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma.探讨外泌体在胰腺导管腺癌的诊断和药物递送中的应用潜力。
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miR-18a and miR-106a Signatures in Plasma Small EVs Are Promising Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma.血浆小细胞外囊泡中的 miR-18a 和 miR-106a 特征可作为胰腺导管腺癌早期检测的有前途的生物标志物。
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Small RNA sequencing analysis of peptide-affinity isolated plasma extracellular vesicles distinguishes pancreatic cancer patients from non-affected individuals.肽亲和分离血浆细胞外囊泡的小 RNA 测序分析可区分胰腺癌患者与非患者。
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A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment.外泌体和 microRNAs 在胰腺癌中作用的最新概述:诊断和治疗的前瞻性计划。
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Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma.血浆细胞外囊泡信使 RNA 分析鉴定出用于胰腺导管腺癌患者生存预测的非侵入性风险分层的预后 EV 标志物。
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Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics.通过蛋白质组学鉴定细胞外囊泡中的癌细胞系特异性蛋白图谱。
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From tumor microenvironment communicants to biomarker discovery: Selectively packaged extracellular vesicular cargoes in pancreatic cancer.从肿瘤微环境交流者到生物标志物发现:胰腺癌中选择性包装的细胞外囊泡货物
Cytokine Growth Factor Rev. 2020 Feb;51:61-68. doi: 10.1016/j.cytogfr.2020.01.001. Epub 2020 Jan 11.

引用本文的文献

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Updates in the diagnosis and management of ductal adenocarcinoma of the pancreas.胰腺导管腺癌诊断与管理的进展
World J Clin Oncol. 2025 Jun 24;16(6):105601. doi: 10.5306/wjco.v16.i6.105601.
2
Composition, functions, and applications of exosomal membrane proteins.外泌体膜蛋白的组成、功能和应用。
Front Immunol. 2024 Aug 1;15:1408415. doi: 10.3389/fimmu.2024.1408415. eCollection 2024.
3
A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment.
外泌体和 microRNAs 在胰腺癌中作用的最新概述:诊断和治疗的前瞻性计划。
Int J Mol Sci. 2024 Mar 17;25(6):3406. doi: 10.3390/ijms25063406.