The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs' large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.

中文翻译：

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在自然发生的癌症犬中进行临床试验的临床，病理和伦理考虑：加速转化药物开发的比较方法。

比较肿瘤学在转化研究中的作用正受到药物开发商和更大的生物医学研究界的越来越多的关注。具有自发性癌症的宠物犬是重要的且未得到充分利用的转化模型，这是由于犬的体型较大和相对远亲，再加上某些肿瘤组织类型的发生率很高，其生物学，遗传学和组织学上与人类肿瘤相似。在完整的免疫系统中，具有自发性肿瘤的狗自然会产生治疗抗性和自发转移。癌症生物学的这些基本特征通常在诱导或基因工程化的临床前肿瘤模型中缺乏，并且可能导致其较差的预测价值以及相关的肿瘤药物开发中总体高失败率。因此，在患有天然癌症的爱犬中进行临床试验代表了可行的替代方法和有价值的中介步骤，应逐步将其纳入癌症药物的发现和开发流程中。分子靶向疗法的发展导致病理学家在人体肿瘤试验中的作用不断扩大，同样，兽医病理学家的专业知识对于比较肿瘤学试验设计和实施的各个阶段将越来越有价值。在这篇评论中，我们提供了一个临床，道德，