Gundert-Remy Ursula, Dimovski Aleksandar, Gajović Srećko
Charite Universitätsmedizin Berlin, Institute for Clinical Pharmacology and Toxicology, Berlin, Germany.
Croat Med J. 2012 Aug;53(4):314-20. doi: 10.3325/cmj.2012.53.314.
Reviewing the past and the present status of personalized medicine, the hope and promise from several years ago was critically compared to what is really achieved to tailor the drug treatment according to the patient's individuality. The basis for consideration is what we know about the variant of the disease the patient is suffering from, and about the mechanisms influencing the plasma concentration-time profile, such as activity of metabolizing enzymes and transporters. In cancer treatment, drugs are currently selected regarding molecular properties of the cancer tissue, eg, expressing receptors such as HER2 receptor. Currently diagnostic tests are available allowing to detect somatic cell mutations that can be used to guide drug selection. Unfortunately, tumor heterogeneity and developing resistance by further mutations may limit the success of the therapy determined by molecular diagnostics. The present status can be described that in drug kinetics we know the influencing factors and we understand the mechanisms. However, only in a few cases the genetic background is the main determinant of kinetic variability, and environmental and other factors have an additional important role. Therefore, much more has to be done before we can translate the accumulating knowledge into a benefit for the patient. Only then, we can speak about personalized medicine.
回顾个性化医疗的过去和现状,将几年前的希望和承诺与根据患者个体情况定制药物治疗的实际成果进行了批判性比较。考虑的基础是我们对患者所患疾病变体的了解,以及对影响血浆浓度-时间曲线的机制的了解,例如代谢酶和转运体的活性。在癌症治疗中,目前根据癌症组织的分子特性选择药物,例如表达HER2受体等受体。目前有诊断测试可用于检测可用于指导药物选择的体细胞突变。不幸的是,肿瘤异质性和进一步突变导致的耐药性可能会限制分子诊断所确定的治疗成功率。目前的状况可以描述为,在药物动力学方面,我们知道影响因素并且理解其机制。然而,只有在少数情况下,遗传背景才是动力学变异性的主要决定因素,环境和其他因素也起着重要作用。因此,在我们能够将积累的知识转化为对患者的益处之前,还有很多工作要做。只有到那时,我们才能谈论个性化医疗。