Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
J Nucl Med. 2010 Apr;51(4):501-4. doi: 10.2967/jnumed.109.065706. Epub 2010 Mar 17.
Animal models have been instrumental in elucidating key biochemical and physiologic processes of cancer onset and propagation in a living organism. Most importantly, they have served as a surrogate for patients in the evaluation of novel diagnostic and therapeutic anticancer drugs, including radiopharmaceuticals. Experimental tumors raised in rodents constitute the major preclinical tool of new-agent screening before clinical testing. Such models for oncologic applications today include solid tumors raised in syngeneic fully immunocompetent hosts and human xenografts induced in immunodeficient mouse strains, and tumors spontaneously growing in genetically engineered mice represent the newest front-line experimental modality. The power of these models to predict clinical efficacy is a matter of dispute, as each model presents inherent strengths and weaknesses in faithfully mirroring the extremely complex process of human carcinogenesis. Differences in size and physiology, as well as variations in the homology of targets between mice and humans, may lead to translational limitations. Other factors affecting the predictive power of preclinical models may be animal handling during experimentation and suboptimal compilation and interpretation of preclinical data. However, animal models will remain a unique source of in vivo information and the irreplaceable link between in vitro studies and our patients.
动物模型在阐明癌症发生和在生物体中传播的关键生化和生理过程方面发挥了重要作用。最重要的是,它们在评估新型诊断和治疗癌症药物(包括放射性药物)方面,已经成为患者的替代物。在啮齿动物中培养的实验肿瘤构成了临床前筛选新药物的主要工具。目前用于肿瘤学应用的模型包括在同源、完全免疫功能正常的宿主中产生的实体瘤和在免疫缺陷小鼠品系中诱导的人异种移植物,以及在基因工程小鼠中自发生长的肿瘤,代表了最新的一线实验模式。这些模型预测临床疗效的能力存在争议,因为每个模型在忠实地反映人类致癌过程的极其复杂过程方面都存在固有优势和劣势。大小和生理上的差异,以及小鼠和人类之间目标的同源性差异,可能导致转化限制。影响临床前模型预测能力的其他因素可能是实验期间的动物处理以及临床前数据的编译和解释不理想。然而,动物模型将仍然是体内信息的独特来源,以及体外研究和我们的患者之间不可替代的联系。