Gordon Ira K, Khanna Chand
NCI Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
ILAR J. 2010;51(3):214-20. doi: 10.1093/ilar.51.3.214.
Successful development of novel cancer drugs depends on well-reasoned scientific drug discovery, rigorous preclinical development, and carefully conceived clinical trials. Failure in any of these steps contributes to poor rates of approval for new drugs to treat cancer. As technological and scientific advances have opened the door to a variety of novel approaches to cancer drug discovery and development, preclinical models that can answer questions about the activity and safety of novel therapies are increasingly necessary. The advance of a drug to clinical trials based on information from preclinical models presupposes that the models convey informative data for future use in human patients with cancer. The study of novel cancer drugs using in vitro models is highly controllable, reproducible, relatively inexpensive, and linked to high throughput. However, these models fail to reproduce many of the complex features of human cancer. Mouse models address some of these limitations but have important biological differences from human cancer. The integration of studies using pet dogs with spontaneously occurring tumors as models in the development path can answer questions not adequately addressed in conventional models and is therefore gaining attention and interest in drug development communities. The study of novel cancer drugs in dogs with naturally occurring tumors allows drug assessment in a cancer that shares many fundamental features with the human cancer condition, and thus provides an opportunity to answer questions that inform the cancer drug development path in ways not possible in more conventional models.
新型抗癌药物的成功研发依赖于合理的科学药物发现、严格的临床前开发以及精心设计的临床试验。这些步骤中的任何一个环节出现失误，都会导致抗癌新药的获批率较低。随着技术和科学的进步为抗癌药物的发现和开发带来了各种新方法，能够回答有关新型疗法活性和安全性问题的临床前模型变得越来越必要。基于临床前模型的信息将药物推进到临床试验阶段，前提是这些模型能够提供对未来癌症患者有用的信息数据。使用体外模型研究新型抗癌药物具有高度可控、可重复、相对便宜且与高通量相关的特点。然而，这些模型无法重现人类癌症的许多复杂特征。小鼠模型解决了其中一些局限性，但与人类癌症存在重要的生物学差异。将患有自发性肿瘤的宠物狗作为模型纳入研发路径进行研究，能够回答传统模型未能充分解决的问题，因此在药物研发领域受到了越来越多的关注和兴趣。对患有自然发生肿瘤的狗进行新型抗癌药物研究，可以在与人类癌症状况具有许多基本特征的癌症中进行药物评估，从而提供了一个机会，以传统模型无法做到的方式回答有助于抗癌药物研发路径的问题。
