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

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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.