Swine models for translational oncological research: an evolving landscape and regulatory considerations.
Swine models for translational oncological research: an evolving landscape and regulatory considerations.
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DOI：
10.1007/s00335-021-09907-y
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Tuggle CK
中科院分区：
文献类型：
--
作者：
Boettcher AN;Schachtschneider KM;Schook LB;Tuggle CK
猪生物医学模型在过去十年中越来越受欢迎，特别是在肿瘤学研究中的应用。用于癌症研究的猪模型包括用于异种移植研究的具有严重联合免疫缺陷的猪、能够在体内发展肿瘤的遗传修饰的猪模型以及正常免疫活性的猪。近年来，在临床试验中批准新的肿瘤治疗药物的成功率很低。这些失败的两个主要原因是由于毒性和安全性问题或缺乏疗效。由于所有治疗药物在临床试验之前必须在动物模型中进行测试，因此有机会在新治疗药物的临床前测试阶段扩大评估疗效和毒性特征的能力。大多数临床前体内试验在小鼠、犬和非人灵长类动物中进行。然而，猪模型是癌症研究的替代大型动物模型，与人类的大小，遗传学和生理学相似。此外，人和猪之间的肿瘤发生途径相似，因为转化需要相似的驱动突变。由于其较大的尺寸，原位肿瘤的发展比较小的啮齿动物模型更容易;此外，猪模型也可用于测试新的介入器械和放射学/手术方法。总之，猪是临床前治疗和器械试验的可行选择。该资源的目标是提供关于临床使用的新疗法和器械所需的监管过程的广泛概述，肿瘤治疗反应的跨物种差异，以及提供已开发的可用于临床前试验以满足监管要求的猪肿瘤模型的概述。
Swine biomedical models have been gaining in popularity over the last decade, particularly for applications in oncology research. Swine models for cancer research include pigs that have severe combined immunodeficiency for xenotransplantation studies, genetically modified swine models which are capable of developing tumors in vivo, as well as normal immunocompetent pigs. In recent years, there has been a low success rate for the approval of new oncological therapeutics in clinical trials. The two leading reasons for these failures are either due to toxicity and safety issues or lack of efficacy. As all therapeutics must be tested within animal models prior to clinical testing, there are opportunities to expand the ability to assess efficacy and toxicity profiles within the preclinical testing phases of new therapeutics. Most preclinical in vivo testing is performed in mice, canines, and non-human primates. However, swine models are an alternative large animal model for cancer research with similarity to human size, genetics, and physiology. Additionally, tumorigenesis pathways are similar between human and pigs in that similar driver mutations are required for transformation. Due to their larger size, the development of orthotopic tumors is easier than in smaller rodent models; additionally, porcine models can be harnessed for testing of new interventional devices and radiological/surgical approaches as well. Taken together, swine are a feasible option for preclinical therapeutic and device testing. The goals of this resource are to provide a broad overview on regulatory processes required for new therapeutics and devices for use in the clinic, cross-species differences in oncological therapeutic responses, as well as to provide an overview of swine oncology models that have been developed that could be used for preclinical testing to fulfill regulatory requirements.
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影响因子：
4.6
作者：
Hendricks-Wenger A;Aycock KN;Nagai-Singer MA;Coutermarsh-Ott S;Lorenzo MF;Gannon J;Uh K;Farrell K;Beitel-White N;Brock RM;Simon A;Morrison HA;Tuohy J;Clark-Deener S;Vlaisavljevich E;Davalos RV;Lee K;Allen IC
通讯作者：
Allen IC
影响因子：
4.7
作者：
Boettcher, Adeline N.;Kiupel, Matti;Shapiro, Erik M.
通讯作者：
Shapiro, Erik M.
影响因子：
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作者：
Choi YJ;Kim E;Reza AMMT;Hong K;Song H;Park C;Cho SK;Lee K;Prather RS;Kim JH
通讯作者：
Kim JH
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8
作者：
Adam, S. J.;Rund, L. A.;Counter, C. M.
通讯作者：
Counter, C. M.