Soldatos Theodoros G, Jackson David B
Molecular Health GmbH, Kurfuersten Anlage 21, 69115 Heidelberg, Germany.
Healthcare (Basel). 2019 Mar 19;7(1):45. doi: 10.3390/healthcare7010045.
Adverse events are a common and for the most part unavoidable consequence of therapeutic intervention. Nevertheless, available tomes of such data now provide us with an invaluable opportunity to study the relationship between human phenotype and drug-induced protein perturbations within a patient system. Deciphering the molecular basis of such adverse responses is not only paramount to the development of safer drugs but also presents a unique opportunity to dissect disease systems in search of novel response biomarkers, drug targets, and efficacious combination therapies. Inspired by the potential applications of this approach, we first examined adverse event circumstances reported in FAERS and then performed a molecular level interrogation of cancer patient adverse events to investigate the prevalence of drug-drug interactions in the context of patient responses. We discuss avoidable and/or preventable cases and how molecular analytics can help optimize therapeutic use of co-medications. While up to one out of three adverse events in this dataset might be explicable by iatrogenic, patient, and product/device related factors, almost half of the patients in FAERS received multiple drugs and one in four may have experienced effects attributable to drug interactions.
不良事件是治疗干预常见且在很大程度上不可避免的后果。然而，现有的大量此类数据为我们提供了一个宝贵的机会，来研究患者系统中人类表型与药物诱导的蛋白质扰动之间的关系。解读此类不良反应的分子基础不仅对于开发更安全的药物至关重要，而且还提供了一个独特的机会，剖析疾病系统以寻找新的反应生物标志物、药物靶点和有效的联合治疗方法。受此方法潜在应用的启发，我们首先检查了FAERS中报告的不良事件情况，然后对癌症患者的不良事件进行分子水平的询问，以调查患者反应背景下药物相互作用的发生率。我们讨论了可避免和/或可预防的病例，以及分子分析如何有助于优化联合用药的治疗应用。虽然该数据集中高达三分之一的不良事件可能可由医源性、患者及产品/器械相关因素解释，但FAERS中几乎一半的患者接受了多种药物治疗，四分之一的患者可能经历了药物相互作用导致的影响。
