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用于新型药物研发的膀胱癌体外和体内实验模型的挑战。

Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery.

机构信息

a Department of Veterinary Sciences , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.

b Center for Research and Technology of Agro-Environment and Biological Sciences , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.

出版信息

Expert Opin Drug Discov. 2016 Jun;11(6):599-607. doi: 10.1080/17460441.2016.1174690. Epub 2016 Apr 28.

DOI:10.1080/17460441.2016.1174690
PMID:27077499
Abstract

INTRODUCTION

Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.

AREAS COVERED

This paper provides critical information on existing in vitro and in vivo models to screen the efficacy and toxicity of innovative UBC therapies and point out the challenges for new and improved models.

EXPERT OPINION

In our opinion, results obtained with in vitro and in vivo models should be interpreted together, as a set of delicate biological tools that can be used at different stages in the drug discovery process, to address specific questions. With the development of new technologies, new assays and biomarkers are going to play an important role in the study of UBC. The molecular diagnostics and genomic revolution will not only help to develop new drug therapies, but also to achieve tailored therapies.

摘要

简介

膀胱癌(UBC)是泌尿系统中第二常见的恶性肿瘤,也是全球第九大常见癌症,影响 65 岁以上的个体。几项研究已经开始深入了解尿路上皮癌发生的机制,了解抗肿瘤药物耐药的机制,并发现新的抗肿瘤药物。体外和体内模型对于深入了解尿路上皮癌发生机制至关重要。通过这些模型,已经发现了涉及尿路上皮癌发生的各种分子途径,从而能够进行治疗干预。

涵盖领域

本文提供了有关现有体外和体内模型的重要信息,用于筛选创新的 UBC 治疗方法的疗效和毒性,并指出了新的和改进的模型所面临的挑战。

专家意见

在我们看来,应该将体外和体内模型的结果结合起来解释,将其视为一组可以在药物发现过程的不同阶段使用的精细的生物学工具,以解决特定的问题。随着新技术的发展,新的检测方法和生物标志物将在 UBC 的研究中发挥重要作用。分子诊断学和基因组革命不仅有助于开发新的药物治疗方法,还可以实现针对性的治疗。

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Expert Opin Drug Discov. 2016 Jun;11(6):599-607. doi: 10.1080/17460441.2016.1174690. Epub 2016 Apr 28.
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