背景:乳腺癌(BC)是女性最常见的癌症,尽管在治疗方面取得了进展,它代表了全球女性癌症死亡的主要原因。常规的治疗方式显著改善了BC患者的管理,但是亚型异质性,耐药性,肿瘤复发仍然是阻碍BC治疗有效性的主要因素。在这种情况下,基于miRNA(miR)的疗法提供了非常有吸引力的研究领域。然而,在BC治疗中使用基于miR的疗法仍然是一个不发达的话题.因此,本系统综述旨在总结目前关于BC有前景的基于miR的疗法的知识,探索专注于体内实验的原创文章.
方法:目前的系统评价是根据PRISMA指南进行的。全面探索PubMed和EMBASE数据库以执行文章搜索。
结果:纳入并分析了21项符合条件的研究:12项专注于基于miR的抗肿瘤疗法,9项专注于基于miR的转移性疗法。我们在动物模型实验中发现了18种不同的miR作为潜在的治疗分子进行测试。大约90%的选定研究评估了miR在三阴性(TN)-BC小鼠模型中作为治疗剂的效率和安全性。在所有基于miR的疗法中,miR-21是研究最多的,并被提出作为TNBC治疗的潜在抗肿瘤分子。此外,miR-34a和miR-205a似乎是成功的抗肿瘤和抗转移分子。
结论:我们的分析提供了关于miR作为BC治疗分子的当前情景的快照。然而,尽管付出了很多努力,没有一项选定的研究超出了临床前研究,它们在临床实践中的可译性似乎还为时过早。
BACKGROUND: Breast cancer (BC) is the most common cancer in females and despite advances in treatment, it represents the leading cause of cancer mortality in women worldwide. Conventional therapeutic modalities have significantly improved the management of BC patients, but subtype heterogeneity, drug resistance, and tumor relapse remain the major factors to hamper the effectiveness of therapy for BC. In this scenario, miRNA(miR)-based therapeutics offer a very attractive area of study. However, the use of miR-based therapeutics for BC treatment still represents an underdeveloped topic. Therefore, this systematic
review aims at summarizing current knowledge on promising miR-based therapeutics for BC exploring original articles focusing on in vivo experiments.
METHODS: The current systematic
review was performed according to PRISMA guidelines. PubMed and EMBASE databases were comprehensively explored to perform the article search.
RESULTS: Twenty-one eligible studies were included and analyzed: twelve focused on antitumor miR-based therapeutics and nine on metastatic miR-based therapeutics. We found 18 different miRs tested as potential therapeutic molecules in animal model experiments. About 90% of the selected studies evaluate the efficiency and the safety of miRs as therapeutic agents in triple-negative (TN)-BC mouse models. Among all founded miR-based therapeutics, miR-21 emerged to be the most investigated and proposed as a potential antitumoral molecule for TNBC treatment. Besides, miR-34a and miR-205a appeared to be successful antitumoral and antimetastatic molecules.
CONCLUSIONS: Our analysis provides a snapshot of the current scenario regarding the miRs as therapeutic molecules in BC. Nevertheless, despite many efforts, none of the selected studies goes beyond preclinical studies, and their translatability in the clinical practice seems quite premature.