抗肿瘤药物的治疗药物监测研究

尽管治疗药物监测(TDM)已广泛应用于多个疾病治疗领域,但在抗肿瘤药物方面的应用仍较为局限。近年来,抗肿瘤药物的暴露量与其疗效和药物不良反应之间的相关性研究越来越多,这有利于抗肿瘤药物个体化精准给药。本文综述了细胞毒类和靶向性(小分子和大分子)抗肿瘤药物的治疗药物监测现状,为肿瘤药物个体化用药提供参考。     

分子靶向抗肿瘤药物十年历程启迪

本文综合分析近十年来分子靶向抗肿瘤药物的历程,回顾各类分子靶向抗肿瘤药物的特点,提出分子靶向抗肿瘤药物开发中值得关注的几个问题:如药物的毒副作用、耐受性,个体化治疗与生物标志物,以及预测敏感患者生物标志物研究等。     

2010－2012年武汉地区32家医院应用抗肿瘤分子靶向治疗药物分析

目的：分析2010－2012年武汉地区32家医院应用抗肿瘤分子靶向治疗药物状况。方法应用金额排序法和用药频度（ DDDs）排序法,对武汉市32家医院近三年临床使用的抗肿瘤分子靶向治疗药物进行回顾性统计和分析。结果武汉地区抗肿瘤分子靶向治疗药物销售金额与DDDs逐年稳定增长,日均费用（ DDC）相对稳定。各类药品销售金额与DDDs排序趋势一致,国产新药埃克替尼的销售金额及DDDs增长较快。结论2010－2012年武汉地区应用抗肿瘤分子靶向治疗药物状况符合临床应用特点,销售金额及DDDs排序合理。     

2009～2011年武汉地区抗肿瘤分子靶向治疗药物应用分析

目的:了解武汉地区医院抗肿瘤分子靶向治疗药物的使用情况与特点。方法:对武汉地区32家医院2009～2011年抗肿瘤分子靶向治疗药物的应用品种、销售金额、用药频度(DDDs)及日均费用(DDC)等进行回顾性统计和分析。结果:武汉地区抗肿瘤分子靶向治疗药物销售金额与DDDs呈逐年增长趋势,DDC相对稳定。结论:2009～2011年武汉地区抗肿瘤分子靶向治疗药物应用状况和发展趋势较为合理。     

化学合成类靶向抗肿瘤药物的研究进展

非细胞毒性靶向抗肿瘤药物的应用使肿瘤患者的生存质量显著提高,甚至长期带瘤生存也成为可能.随着肿瘤发生机制的逐步揭示,细胞与分子靶向治疗在肿瘤治疗中的作用越来越受到重视,这为肿瘤治疗开辟了新的途径.在这些靶向抗肿瘤药物中,化学合成类药物占多数.对化学合成类靶向抗肿瘤药物的研究进展进行综述.     

细胞毒药物与分子靶向治疗的联合应用

随着新型分子靶向药物的开发，抗肿瘤治疗面临新的挑战。围绕细胞毒和分子靶向药物的联合应用存在诸多争议，特别是关于临床前模型的价值和一些临床试验的设计方案。目前的抗肿瘤治疗已包含了几种具有不同机制的药物，分子靶向治疗的联合应用可能具有协同或拮抗作用。本文将重点阐述应用联合治疗的相关问题，希望通过新型靶向治疗与传统化疗药物的联合应用，为抗肿瘤治疗带来新的契机。     

分子靶向药物个体化肿瘤治疗与网络联合进展

分子靶向药物治疗较传统细胞毒药物治疗癌症专一性强,不良反应小。为能满足临床治疗个体化的需要,应用系统生物–药理学整体治疗的新观念,靶向药物的"network"网络联合治疗方式,为临床肿瘤的治疗提供了新的策略和最有利的化疗方案。本文就分子靶向抗癌药物临床个体化应用及基于肿瘤靶向免疫与肿瘤凋亡相关网络联合治疗肿瘤的新途径进行综述。     

分子靶向抗肿瘤药研究进展

分子靶向抗肿瘤药业已成为恶性肿瘤治疗领域的一个主流研究方向.本综述从药物化学结合结构生物学、转化医学的视角切入,对已上市和处于后期临床的小分子蛋白激酶抑制剂进行系统梳理.重点阐述其中蕴含的药物发现策略、药物演化路径、作用机制和个体化治疗等内容.     

南京军区福州总医院常用抗肿瘤靶向药物浅析

目的 通过对福州总医院常用抗肿瘤靶向药物的分析,了解抗肿瘤靶向药物发展的趋势.方法 分析各类药物的主要成分和药理作用等,了解各类药物的特点,对临床提供一些相关信息.结果抗肿瘤靶向药物治疗已经引起人们足够重视.     

分子靶向抗肿瘤药物的不良反应及其处理对策

目前已有多种分子靶向抗肿瘤药物在我国上市,靶向治疗药物以其显著的疗效和良好的耐受性在临床上得到了广泛的应用,很多恶性肿瘤患者已从中获益。早期快速诊断并采取有效干预措施是改善肿瘤患者预后的重要手段,对改善患者生活质量和提高靶向治疗效果也尤为重要。本文对近年来分子靶向抗肿瘤药物的相关文献进行分析归纳,从皮肤系统、消化系统、循环系统、血液系统等多方面对分子靶向药物的不良反应及其处理对策进行了综述,旨在为国内,临床医药人员的实际工作提供参考借鉴,以期制定良好的治疗方案并减少药物的不良反应。     

Nanotechnology approaches for personalized treatment of multidrug resistant cancers

The efficacy of chemotherapy is substantially limited by the resistance of cancer cells to anticancer drugs that fluctuates significantly in different patients. Under identical chemotherapeutic protocols, some patients may receive relatively ineffective doses of anticancer agents while other individuals obtain excessive amounts of drugs that induce severe adverse side effects on healthy tissues. The current review is focused on an individualized selection of drugs and targets to suppress multidrug resistance. Such selection is based on the molecular characteristics of a tumor from an individual patient that can potentially improve the treatment outcome and bring us closer to an era of personalized medicine.     

Patient-tailored treatments with anti-EGFR monoclonal antibodies in advanced colorectal cancer: KRAS and beyond

Personalized medicine emphasizes the practice of considering individual patient characteristics as opposed to that centered on standards derived from epidemiological studies which, by definition, do not take into account the variability of individuals within a given population. When applied to oncology, personalized medicine is an even more complex concept because it extends the variability beyond the individual patient to the individual tumor. Indeed, the great genotypic and phenotypic variability (both in primary and metastatic sites of cancer) the development of targeted therapies, and the growing availability of biological assays complicate the scenario of personalized medicine in the oncological field. In this paper we review the results of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy in metastatic colorectal cancer (mCRC) in the context of tumor biology, delineating the future prospects of patient-tailored medicine in this area. In particular, we deal with EGFR inhibition by Cetuximab, a chimeric mouse human IgG1 mAb, and panitumumab, a fully human IgG2 mAb. We discuss the clinical impact of anti-EGFR mAbs on wild-type (WT) KRAS mCRC, also taking into account the feasibility of novel multi-marker approaches to treatment decision-making, aimed at increasing the predictive power of pre-therapy biomarkers. Experimental topics and fields of ongoing research, such as targeting microRNAs (miRNAs) with novel anticancer drugs and epigenetics in CRC are also addressed.     

Novel Points of Attack for Targeted Cancer Therapy

New molecular insight reveals novel points of attack for targeted cancer therapy. The recent advances in cancer genomics and novel insight into the complex biology of cancer make the promise of personalized, targeted cancer medicine closer than ever. The massive parallel sequencing endeavours performed by The Cancer Genome Atlas, the International Cancer Genome Consortium and by numerous individual investigators have provided a comprehensive genomic characterization of a wide range of cancers. The joint efforts enabled by the improved sequencing technology have demonstrated that individual cancers comprise mutational repertoires with only a few frequently recurrent driver genes. Thus, the identification of new drug targets and novel drugs have accelerated and renewed the hopes of personalized cancer therapy achieving clinical reality for a wider range of cancers. Together with cost‐effective sequencing technology to perform comprehensive mutational profiling of each individual cancer, this provides the basis for a personalized cancer medicine revolution within the next few years. The aim of this MiniReview is to provide an overview of the history and evolution of targeted cancer therapy, exemplified by molecularly targeted drugs successfully implemented in the clinic. Furthermore, we aim to highlight novel molecular targets for therapeutic intervention, as well as the main present challenges including inter‐ and intratumor heterogeneity and cellular plasticity in addition to the importance of the tumor micro‐environment. Many cancer patients already receive some form of tailored therapy, and recent evidence suggests that novel and highly innovative, targeted approaches are on their way into the clinic.     

我院2010-2012年靶向抗肿瘤药利用分析

目的:了解我院靶向抗肿瘤药使用情况,为临床合理用药提供参考依据。方法:采用回顾性调查方法,对我院2010-2012年靶向抗肿瘤药消耗金额、用药频度(DDDs)、日均费用(DDC)及排序比(B/A)进行分析。结果:单分子抗体(Mab)占靶向抗肿瘤药用药金额的72.2%⁷5.5%,小分子受体酪氨酸激酶抑制剂(TKI)占20.1%75.5%,小分子受体酪氨酸激酶抑制剂(TKI)占20.1%²7.1%;靶向抗肿瘤药年用药金额逐年增加,但占抗肿瘤药物的比例逐年下降;2010、2011年分别有3种靶向抗肿瘤药B/A<1,2012年所有靶向抗肿瘤药B/A均≥1。结论:我院靶向抗肿瘤药的应用基本合理,且社会效益和经济效益同步性良好。     

Impact of genetic diagnostics on drug development strategy

Innovation in diagnostics will be essential for the successful adoption of personalized medicine and will also have a major impact on the success of drug development strategies. To remain competitive, companies will need to embrace the rapid innovation in the diagnostic market, utilize diagnostic tools concurrently with research and development, and re-invent how new drugs are brought to market. In this article, specific examples of targeted oncology drugs are used to illustrate the general impact of genetic diagnostics on drug development.     

中草药中发现新抗癌药物的途径

中草药的使用已有数千年的历史,对于各种疾病包括肿瘤的治疗都取得了十分宝贵的人体经验.丰富的中草药资源也为寻找新抗癌药提供了重要的物质基础.从传统中医药理论结合现代科学发现从4个方面阐述了进一步从中草药中发现新抗癌药的途径,以期对天然产物来源的新抗癌药物的发现起到一定的启发与促进作用.这4个方面分别是:根据传统中医理论发现抗癌药,包括清热解毒药、活血化瘀药、调节免疫药(补气扶正药)及有毒中草药(以毒攻毒);从近年发现的抗肿瘤先导化合物中寻找;通过普筛或高通量筛选从中草药提取物中寻找和依据药用植物亲缘学的原理寻找.     

Ethnic differences in the metabolism, toxicology and efficacy of three anticancer drugs

INTRODUCTION: Large inter-individual and inter-ethnic differences are observed in efficacies and toxicities of medical drugs. To improve the predictability of these differences, pharmacogenetic information has been applied to clinical situations. Expanding pharmacogenetic information would be a valuable tool to the medical community as well as the patient to fulfill the promise of personalized anticancer drug therapy. AREAS COVERED: This review highlights genetic polymorphisms and ethnic differences of genes, UGT1As, CYP3A4, CES1As, ABCB1, ABCC2, ABCG2, SLCO1B1, CDA and CYP2D6, involved in metabolism and disposition of three anticancer drugs: irinotecan, gemcitabine and tamoxifen. EXPERT OPINION: Recent pharmacogenetic studies have successfully identified distinct ethnic differences in genetic polymorphisms that are potentially involved in efficacies and toxicities of anticancer drugs. This achievement has led to personalized irinotecan therapy, reflecting ethnic differences in UGT1A1 genotypes, and possible benefits of genetic testing have also been suggested for gemcitabine and tamoxifen therapy, which still requires further validation. The ultimate goal for patients is a high rate or even perfect prediction of efficacies and toxicities of anticancer drugs in each ethnic population. For this challenge, more clinical studies combined with comprehensive omics approaches are necessary to further advance the field.     

PDX模型在肺癌靶向治疗中的应用进展★

肺癌是最常见的肿瘤之一，也是全球癌症死亡的主要原因。近几十年来，肺癌治疗药物的研发及新的肺癌早期诊断生物标志物的开发都取得了重大进展，但传统的临床前模型即细胞系模型用于肺癌诊断和后期疗效评估仍有许多不足。目前，肺癌的临床前研究主要依赖患者来源的肿瘤异种移植（PDX）模型进行药物筛选、联合临床试验和个性化医疗策略的临床前评估。本文概述了PDX模型的建立及其特征，并讨论了其在肺癌临床前治疗中的应用。     

肿瘤药物基因组学研究进展

药物基因组学对于解释药物反应的个体差异及开展个体化用药具有重要意义。近年来药物基因组学新技术在肿瘤药物治疗方面的进展和应用鉴定出多种影响肿瘤药物治疗的遗传变异,深刻影响肿瘤治疗的药物研发及个体化治疗。本文通过举例说明近期肿瘤药物基因组学重要研究进展的临床应用评价及面临的挑战,对肿瘤药物基因组学的发展及其临床应用进行综述。     

药物微生物组学:肠道微生物与个体化用药

药物的安全性与有效性是临床治疗中的关键问题,大量研究表明,人体微生物与药物的疗效、不良反应等显著相关。随着人类微生物组计划的实施,药物微生物组学成为当前生命科学和医学的研究热点。药物微生物组学是药物基因组学的重要扩展和补充,致力于研究药物与微生物之间的相互作用及其与药物效应之间的关系。药物微生物组学研究尚处于起步阶段,其发展将为个体化医学和精准医疗提供必要参考。简介药物微生物组学的发展,并对肠道菌群与个体化用药的国内外研究现状进行综述。