Department of Neurology, Saint Andrew's State General Hospital of Patras, Tsertidou 1 Street, 26335, Patras, Greece.
Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO l'Hospitalet, Bellvitge Institute for Biomedical Research (IDIBELL), Hospital Duran i Reynals, 3a planta, Gran Via de l'Hospitalet 199, 08908 Hospitalet de Llobregat, Barcelona, Spain.
Nat Rev Neurol. 2017 Aug;13(8):492-504. doi: 10.1038/nrneurol.2017.88. Epub 2017 Jun 30.
The increasing availability of sophisticated methods to characterize human genetic variation has enabled pharmacogenetic data to be used not only to predict responses to treatment (in the context of so-called personalized medicine), but also to identify patients at high or low risk of specific treatment-related adverse effects. Over the past two decades, extensive attempts have been made to understand the genetic basis of chemotherapy-induced peripheral neurotoxicity (CIPN), one of the most severe non-haematological adverse effects of cancer treatment. Despite substantial efforts, however, the identification of a genetic profile that can detect patients at high risk of CIPN still represents an unmet need, as the information obtained from pharmacogenetic studies published so far is inconsistent at best. Among the reasons for these inconsistencies, methodological flaws and the poor reliability of existing tools for assessing CIPN features and severity are particularly relevant. This Review provides a critical update of the pharmacogenetics of CIPN, focusing on the studies published since 2011. Strategies for improving the reliability of future pharmacogenetic studies of CIPN are also discussed.
日益复杂的人类遗传变异特征分析方法，不仅使药物遗传学数据可用于预测治疗反应（在所谓的“个体化医疗”背景下），还可用于识别特定治疗相关不良事件高风险或低风险的患者。在过去的二十年中，人们进行了广泛的尝试，以了解化疗引起的周围神经毒性（CIPN）的遗传基础，这是癌症治疗中最严重的非血液学不良事件之一。然而，尽管付出了巨大的努力，但确定能够检测到 CIPN 高风险患者的遗传特征仍然是一个未满足的需求，因为迄今为止发表的药物遗传学研究获得的信息充其量也是不一致的。导致这些不一致的原因中，方法学缺陷以及现有用于评估 CIPN 特征和严重程度的工具的可靠性较差，尤为突出。本文批判性地综述了 CIPN 的药物遗传学，重点关注 2011 年以来发表的研究。还讨论了提高未来 CIPN 药物遗传学研究可靠性的策略。
