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摘要
背景:靶向治疗的药物主要是小分子抑制剂(SMI),单克隆抗体(mAb),干扰RNA分子和microRNA。这些新剂的使用在这些药物的药代动力学(PK)中产生了多方面的步骤。个体PK变异性通常较大,并且在对患者药物遗传学特征(例如细胞色素P450酶)的反应中观察到不可预测性,患者特征例如对治疗的依从性和环境因素。 目的:本综述旨在概述最新的抗肿瘤药物,可用于靶向治疗以及药物基因组学最新发现,涉及单个基因多态性或癌细胞获得性突变的毒性/耐药性。此外,还考虑了基因分型成本和方法的早期概要评估。 未来展望:迄今为止,重要的科学证据尚未支持mAbs和SMI的治疗药物监测(TDM)。为了更好地定义浓度 - 效应关系并进行经典给药与PK导向适应性给药的比较随机试验,应该对目标疗法进行大量的努力。个体药物基因组学概况的检测可能是肿瘤学家的关键,这些肿瘤学家将拥有新的资源来为他们的患者做出治疗决定,从而最大限度地获益并最大限度地降低毒性。基于这一目的,临床医师应评估优化和限制,在成本和适用性方面,执行量身定制的治疗最合适的药理学方法。
关键词: 抗癌单克隆抗体,个性化药物,药物基因组学,定制治疗,酪氨酸激酶抑制剂,癌细胞
Current Cancer Drug Targets
Title:Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Volume: 18 Issue: 5
关键词: 抗癌单克隆抗体,个性化药物,药物基因组学,定制治疗,酪氨酸激酶抑制剂,癌细胞
摘要: Background: 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.
Objective: 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.
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Cite this article as:
Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy, Current Cancer Drug Targets 2018; 18 (5) . https://dx.doi.org/10.2174/1568009617666170208162841
DOI https://dx.doi.org/10.2174/1568009617666170208162841 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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