Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Curr Cancer Drug Targets. 2018;18(5):499-511. doi: 10.2174/1568009617666170208162841.
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors.
This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance of either individual gene polymorphisms or acquired mutation in a cancer cell. In addition, an early outline evaluation of the genotyping costs and methods has been taken into consideration. Future Outlook: To date, therapeutic drug monitoring (TDM) of mAbs and SMIs is not yet supported by heavy scientific evidence. Extensive effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomized trials of classic dosing versus PK-guided adaptive dosing. The detection of individual pharmacogenomics profile could be the key for the oncologists that will have new resources to make treatment decisions for their patients in order to maximize the benefit and minimize the toxicity. Based on this purpose, the clinician should evaluate advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacological approach to performing a tailored therapy.
靶向治疗药物主要包括小分子抑制剂（SMIs）、单克隆抗体（mAbs）、干扰 RNA 分子和 microRNA。这些新药物的使用在药物代谢动力学（PK）方面产生了多方面的变化。个体 PK 变异性通常较大，并且对患者药物遗传学特征（如细胞色素 P450 酶）、患者特征（如治疗依从性）和环境因素的反应存在不可预测性。
本综述旨在概述最新的适用于靶向治疗的抗癌药物，以及与毒性/耐药性相关的最新药物遗传学发现，包括个体基因多态性或癌细胞获得性突变。此外，还考虑了基因分型成本和方法的早期概述评估。
迄今为止，针对 mAbs 和 SMIs 的治疗药物监测（TDM）尚未得到大量科学证据的支持。应大力开展靶向治疗，以更好地定义浓度-效应关系，并进行经典剂量与 PK 指导的适应性剂量比较随机试验。个体药物遗传学特征的检测可能是肿瘤学家的关键，他们将有新的资源来为患者做出治疗决策，以最大程度地提高疗效并最小化毒性。基于这一目的，临床医生应评估最适合进行个体化治疗的药理学方法的优势和局限性，包括成本和适用性。
