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细胞外囊泡在前列腺癌耐药中的诊断和预后意义:文献系统评价。

Diagnostic and prognostic significance of extracellular vesicles in prostate cancer drug resistance: A systematic review of the literature.

机构信息

IRCCS SYNLAB SDN S.p.A., 80131, Napoli, Italy.

出版信息

Prostate Cancer Prostatic Dis. 2023 Jun;26(2):228-239. doi: 10.1038/s41391-022-00521-w. Epub 2022 Mar 9.

DOI:10.1038/s41391-022-00521-w
PMID:35264776
Abstract

BACKGROUND

The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy. However, a fraction of men relapse after initial treatment because they develop drug resistance. The failure of anticancer drugs leaves resistant cancer cells to survive and proliferate, negatively affecting patient survival. Thus, drug resistance remains a significant obstacle to the effective treatment of prostate cancer patients. In this scenario, the involvement of extracellular vesicles (EVs) in intrinsic and acquired resistance have been reported in several tumors, and accumulating data suggests that their differential content can be used as diagnostic or prognostic factors. Thus, we propose a systematic study of literature to provide a snapshot of the current scenario regarding EVs as diagnostic and prognostic biomarkers resource in resistant prostate cancer.

METHODS

We performed the current systematic review according to PRISMA guidelines and comprehensively explored PubMed, EMBASE and Google Scholar databases to achieve the article search.

RESULTS

Thirty-three studies were included and investigated. Among all systematically reviewed EV biomarkers, we found mainly molecules with prognostic significance (61%), molecules with diagnostic relevance (18%), and molecules that serve both purposes (21%). Moreover, among all analyzed molecules isolated from EVs, proteins, mRNAs, and miRNAs emerged to be the most investigated and proposed as potential tools to diagnose or predict resistance/sensitivity to advanced PCa treatments.

DISCUSSION

Our analysis provides a snapshot of the current scenario regarding EVs as potential clinical biomarkers in resistant PCa. Nevertheless, despite many efforts, the use of EV biomarkers in PCa is currently at an early stage: none of the selected EV biomarkers goes beyond preclinical studies, and their translatability is yet far from clinical settings.

摘要

背景

前列腺癌的临床行为具有高度异质性,大多数患者被诊断为局部疾病,这些疾病通过手术或放疗成功得到治疗。然而,一部分患者在初始治疗后会复发,因为他们产生了耐药性。抗癌药物的失败使耐药癌细胞得以存活和增殖,从而对患者的生存产生负面影响。因此,耐药性仍然是有效治疗前列腺癌患者的重大障碍。在这种情况下,已经有研究报道了细胞外囊泡(EVs)在几种肿瘤中的内在和获得性耐药中的作用,并且越来越多的数据表明,它们的差异内容可以用作诊断或预后因素。因此,我们建议对文献进行系统研究,以提供当前关于 EVs 作为耐药性前列腺癌诊断和预后生物标志物资源的情况快照。

方法

我们根据 PRISMA 指南进行了当前的系统评价,并全面探索了 PubMed、EMBASE 和 Google Scholar 数据库以实现文章搜索。

结果

共纳入 33 项研究,并进行了系统评价。在所有系统评价的 EV 生物标志物中,我们主要发现了具有预后意义的分子(61%)、具有诊断相关性的分子(18%)和具有双重作用的分子(21%)。此外,在所分析的源自 EV 的所有分子中,蛋白质、mRNAs 和 miRNAs 被认为是最受关注的,并被提出作为潜在的诊断或预测耐药/对晚期前列腺癌治疗敏感性的工具。

讨论

我们的分析提供了当前关于 EVs 作为耐药性前列腺癌潜在临床生物标志物的情况快照。然而,尽管做出了许多努力,但 EV 生物标志物在前列腺癌中的应用目前仍处于早期阶段:所选的 EV 生物标志物没有一个超出了临床前研究,其可转化性还远远没有达到临床环境。

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Sci Rep. 2021 Apr 15;11(1):8279. doi: 10.1038/s41598-021-87441-2.
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Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles from the Metastatic Prostate Cancer Bone Microenvironment.镭-223 治疗可增加转移性前列腺癌骨微环境细胞外囊泡中的免疫检查点表达。
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YAP1 overexpression contributes to the development of enzalutamide resistance by induction of cancer stemness and lipid metabolism in prostate cancer.
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Biomolecules. 2024 Dec 27;15(1):23. doi: 10.3390/biom15010023.
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Assessing the Efficacy of Anti-Cancer Drugs on Organoid Models Derived from Prostate Cancer.评估抗癌药物对前列腺癌类器官模型的疗效。
Dokl Biochem Biophys. 2023 Dec;513(Suppl 1):S96-S99. doi: 10.1134/S1607672923700692. Epub 2024 Feb 9.
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