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创新仪器平台助力淋巴瘤的精准医学

Precision Medicine in Lymphoma by Innovative Instrumental Platforms.

作者信息

Di Paolo Antonello, Arrigoni Elena, Luci Giacomo, Cucchiara Federico, Danesi Romano, Galimberti Sara

机构信息

Section of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Unit of Clinical Pharmacology and Pharmacogenetics, Pisa University Hospital, Pisa, Italy.

出版信息

Front Oncol. 2019 Dec 17;9:1417. doi: 10.3389/fonc.2019.01417. eCollection 2019.

Abstract

In recent years, many efforts have been addressed to the growing field of precision medicine in order to offer individual treatments to every patient on the basis of his/her genetic background. Formerly adopted to achieve new disease classifications as it is still done, innovative platforms, such as microarrays, genome-wide association studies (GWAS), and next generation sequencing (NGS), have made the progress in pharmacogenetics faster and cheaper than previously expected. Several studies in lymphoma patients have demonstrated that these platforms can be used to identify biomarkers predictive of drug efficacy and tolerability, discovering new possible druggable proteins. Indeed, GWAS and NGS allow the investigation of the human genome, finding interesting associations with putative or unexpected targets, which in turns may represent new therapeutic possibilities. Importantly, some objective difficulties have initially hampered the translation of findings in clinical routines, such as the poor quantity/quality of genetic material or the paucity of targets that could be investigated at the same time. At present, some of these technical issues have been partially solved. Furthermore, these analyses are growing in parallel with the development of bioinformatics and its capabilities to manage and analyze big data. Because of pharmacogenetic markers may become important during drug development, regulatory authorities (i.e., EMA, FDA) are preparing guidelines and recommendations to include the evaluation of genetic markers in clinical trials. Concerns and difficulties for the adoption of genetic testing in routine are still present, as well as affordability, reliability and the poor confidence of some patients for these tests. However, genetic testing based on predictive markers may offers many advantages to caregivers and patients and their introduction in clinical routine is justified.

摘要

近年来,为了基于每位患者的基因背景提供个性化治疗,人们在精准医学这一不断发展的领域付出了诸多努力。创新平台,如微阵列、全基因组关联研究(GWAS)和下一代测序(NGS),以前用于实现新的疾病分类(现在仍在这样做),它们使药物遗传学的进展比预期更快且成本更低。对淋巴瘤患者的多项研究表明,这些平台可用于识别预测药物疗效和耐受性的生物标志物,发现新的可能的可成药蛋白。事实上,GWAS和NGS能够对人类基因组进行研究,发现与推定或意外靶点的有趣关联,进而可能代表新的治疗可能性。重要的是,一些客观困难最初阻碍了研究结果在临床常规中的转化,比如遗传物质的数量/质量不佳,或者可同时研究的靶点较少。目前,其中一些技术问题已得到部分解决。此外,这些分析与生物信息学及其管理和分析大数据能力的发展同步增长。由于药物遗传学标志物在药物研发过程中可能变得很重要,监管机构(如欧洲药品管理局、美国食品药品监督管理局)正在制定指南和建议,以便在临床试验中纳入对遗传标志物的评估。在常规应用中采用基因检测仍存在担忧和困难,还有可承受性、可靠性以及一些患者对这些检测的信心不足等问题。然而,基于预测性标志物的基因检测可能会给医护人员和患者带来诸多益处,将其引入临床常规是合理的。

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