Angerilli Valentina, Galuppini Francesca, Businello Gianluca, Dal Santo Luca, Savarino Edoardo, Realdon Stefano, Guzzardo Vincenza, Nicolè Lorenzo, Lazzarin Vanni, Lonardi Sara, Loupakis Fotios, Fassan Matteo
Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, 35100 Padua, Italy.
Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35100 Padua, Italy.
Biomedicines. 2021 Mar 21;9(3):318. doi: 10.3390/biomedicines9030318.
The advent of precision therapies against specific gene alterations characterizing different neoplasms is revolutionizing the oncology field, opening novel treatment scenarios. However, the onset of resistance mechanisms put in place by the tumor is increasingly emerging, making the use of these drugs ineffective over time. Therefore, the search for indicators that can monitor the development of resistance mechanisms and above all ways to overcome it, is increasingly important. In this scenario, microRNAs are ideal candidate biomarkers, being crucial post-transcriptional regulators of gene expression with a well-known role in mediating mechanisms of drug resistance. Moreover, as microRNAs are stable molecules, easily detectable in tissues and biofluids, they are the ideal candidate biomarker to identify patients with primary resistance to a specific targeted therapy and those who have developed acquired resistance. The aim of this review is to summarize the major studies that have investigated the role of microRNAs as mediators of resistance to targeted therapies currently in use in gastro-intestinal neoplasms, namely anti-EGFR, anti-HER2 and anti-VEGF antibodies, small-molecule tyrosine kinase inhibitors and immune checkpoint inhibitors. For every microRNA and microRNA signature analyzed, the putative mechanisms underlying drug resistance were outlined and the potential to be translated in clinical practice was evaluated.
针对不同肿瘤所特有的特定基因改变的精准疗法的出现，正在彻底改变肿瘤学领域，开启新的治疗前景。然而，肿瘤所建立的耐药机制的出现日益增多，使得这些药物的使用随着时间推移而失效。因此，寻找能够监测耐药机制发展的指标，尤其是克服耐药性的方法，变得越来越重要。在这种情况下，微小RNA是理想的候选生物标志物，它们是基因表达的关键转录后调节因子，在介导耐药机制中发挥着众所周知的作用。此外，由于微小RNA是稳定的分子，易于在组织和生物流体中检测到，它们是识别对特定靶向治疗具有原发性耐药性的患者以及已产生获得性耐药性患者的理想候选生物标志物。本综述的目的是总结主要研究，这些研究调查了微小RNA作为胃肠道肿瘤目前使用的靶向治疗耐药性介导因子的作用，即抗表皮生长因子受体（EGFR）、抗人表皮生长因子受体2（HER2）和抗血管内皮生长因子（VEGF）抗体、小分子酪氨酸激酶抑制剂和免疫检查点抑制剂。对于分析的每个微小RNA和微小RNA特征，概述了耐药性的潜在机制，并评估了其在临床实践中转化应用的潜力。
