Enhancing the dog as a model for human cancers: from genome sequence towards clinical trials.

总结 家犬作为一种比较自发的动物， 癌症模型，以研究遗传和环境风险因素，以及缓解 啮齿动物和人类临床试验之间的过渡，用于新的癌症治疗。的许多 影响人类和狗的各种癌症类型之间的相似性， 这些癌症在具有免疫能力的犬个体中的自发发展 和我们生活在一个共同的环境中说明了一个共同的病因寿命越短 狗和癌症治疗后复发的时间较短， 新的癌症药物的疗效、短期和长期毒性和副作用， 而不是像人体临床试验那样几十年才能产生。 然而，需要克服某些限制，以充分利用狗模型。 常见癌症的分类系统略有不同，这限制了数据的翻译， 从狗到人的临床结果。狗的基因组和注释，特别是 复杂的免疫基因家族，可以改进，以允许更仔细和正确的 与人类基因组和免疫反应相比，免疫反应是癌症的关键因素， 发展和治疗。 使用新的长读序测序技术，我们将产生铂CanFam 4.0 一个老年健康人的基因组和改进的基因和变异注释信息 德国牧羊犬此外，我们将特别关注犬乳房 肿瘤，淋巴瘤和骨肉瘤，其中改进的模型将使人类受益 研究，和犬的形式是多种多样的，只有部分特点。以来 用于人类癌症的分子亚分类尚未用于这些犬 癌症，我们计划使用几种方法来描述狗群中这些肿瘤类型的特征。 达到人类标准的方法。我们将进一步建立一个全斯堪的纳维亚 兽医肿瘤学网络的研究合作，增加使用狗作为一个 模型我们将对患有恶性乳腺癌的犬进行重复采血 肿瘤，以允许研究肿瘤的演变和进展。所有这些工作将奠定 为未来更有用、更有效的临床试验奠定基础。

SUMMARY The domestic dog has become increasingly useful as a comparative spontaneous cancer model to study genetic and environmental risk factors as well as for easing the transition between rodent and human clinical trials for novel cancer therapies. The many similarities between various cancer types affecting humans and dogs and the spontaneous development of these cancers in immune competent canine individuals living in a shared environment with us suggest a common aetiology. The shorter lifespan of dogs and the shorter time to relapse after cancer treatment allows data regarding efficacy, short and long term toxicity and side effects of novel cancer drugs to be generated in years rather than decades as in human clinical trials. However, certain limitations need to be overcome to make full use of the dog model. Slightly different classification systems for common cancers limit translation of data and clinical outcome from dog to human. The canine genome and annotation, especially that of complex immune gene families, could be improved to allow a more careful and correct comparison with the human genome and immune response, a key factor in cancer development and treatment. Using novel long-read sequencing techniques, we will generate a platinum CanFam4.0 genome and improved information of both gene and variant annotation for an old healthy female German shepherd. In addition, we will specifically focus on canine mammary tumors, lymphoma and osteosarcoma where improved models would benefit human studies, and the canine forms are diverse and only partly characterized. Since the molecular sub-classifications used in human cancers are not yet used for these canine cancers, we plan to characterize these tumor types in the dog population using several approaches to meet human standards. We will further set up a Scandinavian-wide veterinary oncology network for research collaboration, increased use of the dog as a model. We will perform repeated blood sampling from dogs with malignant mammary tumors to allow the study of tumor evolution and progression. All of this work will lay the groundwork to enable more useful and efficient future clinical trials.