Al-Mahayri Zeina N, Patrinos George P, Ali Bassam R
Department of Pathology, College of Medicine & Health Sciences, United Arab Emirates University, United Arab Emirates.
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, Patras, Greece.
Pharmacogenomics. 2017 May;18(7):687-699. doi: 10.2217/pgs-2017-0005. Epub 2017 May 4.
Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence. The most robust pharmacogenomics data are those for thiopurines and methotrexate use, with evidence-based preemptive testing recommendations for the former. Pharmacogenomics has a significant potential utility in pediatric ALL treatment regimens. In this review, gaps and limitations in this field are emphasized, which may provide a useful guide for future research design.
尽管小儿急性淋巴细胞白血病（ALL）治疗取得了重大进展，但药物的不良副作用仍然是一个具有挑战性的问题。已经开展了许多ALL药物基因组学研究，以阐明其发生的易感遗传因素。关于糖皮质激素相关的骨坏死、长春新碱相关的神经毒性以及蒽环类药物相关的心脏毒性，已有合理的药物基因组学数据。然而，由于一些限制，这些数据尚未完全转化为临床应用，最重要的是缺乏可靠的证据。最有力的药物基因组学数据是关于硫嘌呤和甲氨蝶呤使用的数据，前者有基于证据的预先检测建议。药物基因组学在小儿ALL治疗方案中具有显著的潜在应用价值。在本综述中，强调了该领域的差距和局限性，这可能为未来的研究设计提供有用的指导。
