Crisci Stefania, Amitrano Filomena, Saggese Mariangela, Muto Tommaso, Sarno Sabrina, Mele Sara, Vitale Pasquale, Ronga Giuseppina, Berretta Massimiliano, Di Francia Raffaele
Hematology-Oncology and Stem Cell Transplantation Unit, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples 80131, Italy.
Gruppo Oncologico Ricercatori Italiano GORI ONLUS, Pordenone 33100, Italy.
Medicina (Kaunas). 2019 Jul 28;55(8):414. doi: 10.3390/medicina55080414.
The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells' inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.
肿瘤生物学和微环境知识的更新为肿瘤细胞与正常细胞之间的差异提供了信息。因此，针对这些差异的需求促使了对肿瘤细胞内部机制具有活性的新型分子（靶向治疗）的开发。有几种类型的靶向药物，包括小分子抑制剂（SMIs）、单克隆抗体（mAbs）、干扰RNA（iRNA）分子和微小RNA。在临床实践中，这些新药在药代动力学（PK）方面产生了多层次的情况，其中包括广泛的个体PK变异性，以及根据患者的药物遗传学（PG）特征（例如细胞色素P450酶）和患者特征（如对治疗的依从性和环境因素）而产生的不可预测的结果。本综述重点关注靶向药物在癌症血液学的人体I/II/III期临床试验中的应用。因此，它概述了适用于靶向治疗的最新抗癌药物以及与药物反应相关的药物基因组学的最新发现。此外，还讨论了基因分型成本的总结评估。靶向治疗似乎是肿瘤血液学中一种有效且毒性较小的治疗方法。识别个体PG特征应该是肿瘤学家为患者做出治疗决策的新资源，以尽量减少治疗的毒性和/或无效性。这可以使临床医生评估最适合进行量身定制治疗的药理学方法在成本和适用性方面的益处和限制。
