Arbitrio Mariamena, Di Martino Maria Teresa, Scionti Francesca, Barbieri Vito, Pensabene Licia, Tagliaferri Pierosandro
Institute of Neurological Sciences, UOS of Pharmacology, 88100 Catanzaro, Italy.
Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy.
High Throughput. 2018 Dec 18;7(4):40. doi: 10.3390/ht7040040.
In the past decades, many efforts have been made to individualize medical treatments, taking into account molecular profiles and the individual genetic background. The development of molecularly targeted drugs and immunotherapy have revolutionized medical treatments but the inter-patient variability in the anti-tumor drug pharmacokinetics (PK) and pharmacodynamics can be explained, at least in part, by genetic variations in genes encoding drug metabolizing enzymes and transporters (ADME) or in genes encoding drug receptors. Here, we focus on high-throughput technologies applied for PK screening for the identification of predictive biomarkers of efficacy or toxicity in cancer treatment, whose application in clinical practice could promote personalized treatments tailored on individual's genetic make-up. Pharmacogenomic tools have been implemented and the clinical utility of pharmacogenetic screening could increase safety in patients for the identification of drug metabolism-related biomarkers for a personalized medicine. Although pharmacogenomic studies were performed in adult cohorts, pharmacogenetic pediatric research has yielded promising results. Additionally, we discuss the current challenges and theoretical bases for the implementation of pharmacogenetic tests for translation in the clinical practice taking into account that pharmacogenomics platforms are discovery oriented and must open the way for the setting of robust tests suitable for daily practice.
在过去几十年里，人们为实现个体化医疗付出了诸多努力，充分考虑分子特征和个体遗传背景。分子靶向药物和免疫疗法的发展彻底改变了医疗治疗方式，但患者间抗肿瘤药物药代动力学（PK）和药效动力学的差异，至少部分可以由编码药物代谢酶和转运体（ADME）的基因或编码药物受体的基因中的遗传变异来解释。在此，我们聚焦于用于PK筛选的高通量技术，以识别癌症治疗中疗效或毒性的预测生物标志物，其在临床实践中的应用能够推动基于个体基因组成的个性化治疗。药物基因组学工具已得到应用，药物遗传学筛查的临床效用能够提高患者安全性，以识别用于个性化医疗的药物代谢相关生物标志物。尽管药物基因组学研究是在成人队列中进行的，但药物遗传学儿科研究也取得了有前景的结果。此外，考虑到药物基因组学平台以发现为导向，必须为建立适用于日常实践的可靠检测方法开辟道路，我们讨论了在临床实践中实施药物遗传学检测用于转化的当前挑战和理论基础。
